Indazole derivatives for the treatment of hsp90-induced diseases

ABSTRACT

Novel indazole derivatives of the formula (I), in which R 1 -R 3  have the meanings indicated in Claim ( 1 ), are HSP90 inhibitors and can be used for the preparation of a medicament for the treatment of diseases in which the inhibition, regulation and/or modulation of HSP90 plays a role.

BACKGROUND OF THE INVENTION

The invention was based on the object of finding novel compounds havingvaluable properties, in particular those which can be used for thepreparation of medicaments.

The present invention relates to compounds in which the inhibition,regulation and/or modulation of HSP90 plays a role, furthermore topharmaceutical compositions which comprise these compounds, and to theuse of the compounds for the treatment of diseases in which HSP90 playsa role.

The correct folding and conformation of proteins in cells is ensured bymolecular chaperones and is critical for the regulation of theequilibrium between protein synthesis and degradation. Chaperones areimportant for the regulation of many central functions of cells, suchas, for example, cell proliferation and apoptosis (Jolly and Morimoto,2000; Smith et al., 1998; Smith, 2001).

Heat Shock Proteins (HSPs)

The cells of a tissue react to external stress, such as, for example,heat, hypoxia, oxidative stress, or toxic substances, such as heavymetals or alcohols, with activation of a number of chaperones which areknown under the term “heat shock proteins” (HSPs).

The activation of HSPs protects the cell against damage initiated bysuch stress factors, accelerates the restoration of the physiologicalstate and results in a stress-tolerant state of the cell.

Besides this originally discovered protective mechanism promoted by HSPsagainst external stress, further important chaperone functions have alsobeen described in the course of time for individual HSPs under normalstress-free conditions. Thus, various HSPs regulate, for example,correct folding, intracellular localisation and function or regulateddegradation of a number of biologically important proteins of cells.

HSPs form a gene family with individual gene products whose cellularexpression, function and localisation differs in different cells. Thenaming and classification within the family is carried out on the basisof their molecular weight, for example HSP27, HSP70, and HSP90.

Some human diseases are based on incorrect protein folding (see review,for example, Tytell et al., 2001; Smith et al., 1998). The developmentof therapies which engages in the mechanism of the chaperone-dependentprotein folding could therefore be useful in such cases. For example,incorrectly folded proteins result in aggregation of protein withneurodegenerative progression in the case of Alzheimer's disease, priondiseases or Huntington's syndrome. Incorrect protein folding may alsoresult in loss of wild-type function, which can have the consequence ofincorrectly regulated molecular and physiological function.

HSPs are also ascribed great importance in tumour diseases. There are,for example, indications that the expression of certain HSPs correlateswith the stage of progression of tumours (Martin et al., 2000; Conroy etal., 1996; Kawanishi et al., 1999; Jameel et al., 1992; Hoang et al.,2000; Lebeau et al., 1991).

The fact that HSP90 plays a role in a number of central oncogenicsignalling pathways in the cell and certain natural products havingcancer-inhibiting activity target HSP90 has led to the concept thatinhibition of the function of HSP90 would be sensible in the treatmentof tumour diseases. An HSP90 inhibitor,17-allylamino-17-demethoxygeldanamycin (17AAG), a derivative ofgeldanamycin, is currently undergoing clinical trials.

HSP90

HSP90 represents approximately 1-2% of the total cellular protein mass.It is usually in the form of a dimer in the cell and is associated witha multiplicity of proteins, so-called co-chaperones (see, for example,Pratt, 1997). HSP90 is essential for the vitality of cells (Young etal., 2001) and plays a key role in the response to cellular stress byinteraction with many proteins whose native folding has been modified byexternal stress, such as, for example, heat shock, in order to restorethe original folding or to prevent aggregation of the proteins (Smith etal., 1998).

There are also indications that HSP90 is of importance as buffer againstthe effects of mutations, presumably through correction of incorrectprotein folding caused by the mutation (Rutherford and Lindquist, 1998).

In addition, HSP90 also has a regulatory importance. Under physiologicalconditions, HSP90, together with its homologue in the endoplasmaticreticulum, GRP94, plays a role in the cell balance for ensuring thestability of the conformation and maturing of various client keyproteins. These can be divided into three groups: receptors for steroidhormones, Ser/Thr or tyrosine kinases (for example ERBB2, RAF-1, CDK4and LCK) and a collection of various proteins, such as, for example,mutated p53 or the catalytic subunit of telomerase hTERT. Each of theseproteins takes on a key role in the regulation of physiological andbiochemical processes of cells. The preserved HSP90 family in humansconsists of four genes, cytosolic HSP90a, the inducible HSP90β isoform(Hickey et al., 1989), GRP94 in the endoplasmatic reticulum (Argon etal., 1999) and HSP75/TRAP1 in the mitochondrial matrix (Felts et al.,2000). It is assumed that all members of the family have a similar modeof action, but, depending on their localisation in the cell, bind todifferent client proteins. For example, ERBB2 is a specific clientprotein of GRP94 (Argon et al., 1999), while the type 1 receptor oftumour necrosis factor (TNFR1) or the retinoblastoma protein (Rb) havebeen found to be clients of TRAP1 (Song et al., 1995; Chen et al, 1996).

HSP90 is involved in a number of complex interactions with a largenumber of client proteins and regulatory proteins (Smith, 2001).Although precise molecular details have not yet been clarified,biochemical experiments and investigations with the aid of X-raycrystallography in recent years have increasingly been able to decipherdetails of the chaperone function of HSP90 (Prodromou et al., 1997;Stebbins et al., 1997). Accordingly, HSP90 is an ATP-dependent molecularchaperone (Prodromou et al, 1997), with dimerisation being important forATP hydrolysis. The binding of ATP results in the formation of atoroidal dimer structure, in which the two N-terminal domains come intoclose contact with one another and act as a switch in the conformation.(Prodromou and Pearl, 2000).

Known HSP90 Inhibitors

The first class of HSP90 inhibitors to be discovered were benzoquinoneansamycins with the compounds herbimycin A and geldanamycin. Originally,the reversion of the malignant phenotype in fibroblasts which had beeninduced by transformation with the v-Src oncogene was detected with them(Uehara et al., 1985).

Later, a strong antitumoural activity was demonstrated in vitro (Schulteet al., 1998) and in vivo in animal models (Supko et al., 1995).

Immune precipitation and investigations on affinity matrices then showedthat the principal mechanism of action of geldanamycin involves bindingto HSP90 (Whitesell et al., 1994; Schulte and Neckers, 1998). Inaddition, X-ray crystallographic studies have shown that geldanamycincompetes for the ATP binding site and inhibits the intrinsic ATPaseactivity of HSP90 (Prodromou et al., 1997; Panaretou et al., 1998). Thisprevents the formation of the multimeric HSP90 complex, with itsproperty of functioning as chaperone for client proteins. As aconsequence, client proteins are degraded via the ubiquitin-proteasomepathway.

The geldanamycin derivative 17-allylamino-17-demethoxygeldanamycin(17AAG) showed an unchanged property in the inhibition of HSP90, thedegradation of client proteins and antitumoural activity in cellcultures and in xenograft tumour models (Schulte et al, 1998; Kelland etal, 1999), but had significantly lower liver cytotoxicity thangeldanamycin (Page et all 1997). 17AAG is currently undergoing phaseI/II clinical trials.

Radicicol, a macrocyclic antibiotic, likewise exhibited revision of thev-Src and v-Ha-Ras-induced malignant phenotype of fibroblasts (Kwon etall 1992; Zhao et al, 1995). Radicicol degrades a large number of signalproteins as a consequence of HSP90 inhibition (Schulte et al., 1998).X-ray crystallographic studies have shown that radicicol likewise bindsto the N-terminal domain of HSP90 and inhibits the intrinsic ATPaseactivity (Roe et al., 1998).

As is known, antibiotics of the coumarine type bind to the ATP bindingsite of the HSP90 homologue DNA gyrase in bacteria. The coumarine,novobiocin, binds to the carboxy-terminal end of HSP90, i.e. to adifferent site in HSP90 than the benzoquinone-ansamycins and radicicol,which bind to the N-terminal end of HSP90. (Marcu et al. 2000b).

The inhibition of HSP90 by novobiocin results in degradation of a largenumber of HSP90-dependent signal proteins (Marcu et al., 2000a).

The degradation of signal proteins, for example ERBB2, was demonstratedusing PU3, an HSP90 inhibitor derived from purines. PU3 causes cellcycle arrest and differentiation in breast cancer cell lines (Chiosis etal., 2001).

HSP90 as Therapeutic Target

Due to the participation of HSP90 in the regulation of a large number ofsignalling pathways which are of crucial importance in the phenotype ofa tumour, and the discovery that certain natural products exert theirbiological effect through inhibition of the activity of HSP90, HSP90 iscurrently being tested as a novel target for the development of a tumourtherapeutic agent (Neckers et al., 1999).

The principal mechanism of action of geldanamycin, 17AAG, and radicicolincludes the inhibition of the binding of ATP to the ATP binding site atthe N-terminal end of the protein and the resultant inhibition of theintrinsic ATPase activity of HSP90 (see, for example, Prodromou et al.,1997; Stebbins et al., 1997; Panaretou et al., 1998). Inhibition of theATPase activity of HSP90 prevents the recruitment of co-chaperones andfavours the formation of an HSP90 heterocomplex, which causes clientproteins to undergo degradation via the ubiquitin-proteasome pathway(see, for example, Neckers et al., 1999; Kelland et al., 1999). Thetreatment of tumour cells with HSP90 inhibitors results in selectivedegradation of important proteins having fundamental importance forprocesses such as cell proliferation, regulation of the cell cycle andapoptosis. These processes are frequently deregulated in tumours (see,for example, Hostein et al., 2001).

An attractive rationale for the development of an inhibitor of HSP90 isthat a strong tumour-therapeutic action can be achieved by simultaneousdegradation of a plurality of proteins which are associated with thetrans-formed phenotype.

In detail, the present invention relates to compounds which inhibit,regulate and/or modulate HSP90, to compositions which comprise thesecompounds, and to methods for the use thereof for the treatment ofHSP90-induced diseases, such as tumour diseases, viral diseases, suchas, for example, hepatitis B (Waxman, 2002); immune suppression intransplants (Bijlmakers, 2000 and Yorgin, 2000); inflammation-induceddiseases (Bucci, 2000), such as rheumatoid arthritis, asthma, multiplesclerosis, type 1 diabetes, lupus erythematosus, psoriasis andinflammatory bowel disease; cystic fibrosis (Fuller, 2000); diseasesassociated with angiogenesis (Hur, 2002 and Kurebayashi, 2001), such as,for example, diabetic retinopathy, haemangiomas, endometriosis andtumour angiogenesis; infectious diseases; autoimmune diseases;ischaemia; promotion of nerve regeneration (Rosen et al., WO 02/09696,Degranco et al., WO 99/51223; Gold, U.S. Pat. No. 6,210,974 B1);fibrogenetic diseases, such as, for example, scierodermatitis,polymyositis, systemic lupus, cirrhosis of the liver, keloid formation,interstitial nephritis and pulmonary fibrosis (Strehlow, WO 02/02123).

The invention also relates to the use of the compounds according to theinvention for the protection of normal cells against toxicity caused bychemotherapy, and to the use in diseases where incorrect protein foldingor aggregation is a principal causal factor, such as, for example,scrapie, Creutzfeldt-Jakob disease, Huntington's or Alzheimer's(Sittler, Hum. Mol. Genet., 10, 1307, 2001; Tratzelt et al., Proc. Nat.Acad. Sci., 92, 2944, 1995; Winklhofer et al., J. Biol. Chem., 276,45160, 2001).

WO 01/72779 describes purine compounds and the use thereof for thetreatment of GRP94 (homologue or paralogue of HSP90)-induced diseases,such as tumour diseases, where the cancerous tissue includes a sarcomaor carcinoma selected from the group consisting of fibrosarcoma,myxosarcoma, liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma,angiosarcoma, endotheliosarcoma, lymphangiosarcoma,lymphangioendotheliosarcoma, synovioma, mesothelioma, Ewing's tumour,leiosarcoma, rhabdomyosarcoma, colon carcinoma, pancreatic cancer,breast cancer, ovarian cancer, prostate cancer, squamous cell carcinoma,basal cell carcinoma, adenocarcinoma, syringocarcinoma, sebaceous glandcarcinoma, papillary carcinoma, papillary adenocarcinomas,cystadenocarcinomas, bone marrow carcinoma, bronchogenic carcinoma,renal cell carcinoma, hepatoma, bile duct carcinoma, choriocarcinoma,seminoma, embryonic carcinoma, Wilm's tumour, cervical cancer,testicular tumour, lung carcinoma, small-cell lung carcinoma, bladdercarcinoma, epithelial carcinoma, glioma, astrocytoma, medulloblastoma,craniopharyngioma, ependymoma, pinealoma, haemangioblastoma, acousticneuroma, oligodendroglioma, meningioma, melanoma, neuroblastoma,retinoblastoma, leukaemia, lymphoma, multiple myeloma, Waldenstrom'smacroglobulinaemia and heavy chain disease.

WO 01/72779 furthermore discloses the use of the compounds mentionedtherein for the treatment of viral diseases, where the viral pathogen isselected from the group consisting of hepatitis type A, hepatitis typeB, hepatitis type C, influenza, varicella, adenovirus, herpes simplextype I (HSV-1), herpes simplex type II (HSV-II), cattle plague,rhinovirus, echovirus, rotavirus, respiratory syncytial virus (RSV),papillomavirus, papovavirus, cytomegalovirus, echinovirus, arbovirus,huntavirus, Coxsackie virus, mumps virus, measles virus, rubella virus,polio virus, human immunodeficiency virus type I (HIV-I) and humanimmunodeficiency virus type II (HIV-II).

WO 01/72779 furthermore describes the use of the compounds mentionedtherein for GRP94 modulation, where the modulated biological GRP94activity causes an immune reaction in an individual, protein transportfrom the endoplasmatic reticulum, recovery from hypoxic/anoxic stress,recovery from malnutrition, recovery from heat stress, or combinationsthereof, and/or where the disorder is a type of cancer, an infectiousdisease, a disorder associated with disrupted protein transport from theendoplasmatic reticulum, a disorder associated withischaemia/reperfusion, or combinations thereof, where the disorderassociated with ischaemia/reperfusion is a consequence of cardiacarrest, asystolia and delayed ventricular arrhythmia, heart operation,cardiopulmonary bypass operation, organ transplant, spinal cord trauma,head trauma, stroke, thromboembolic stroke, haemorrhagic stroke,cerebral vasospasm, hypotonia, hypoglycaemia, status epilepticus, anepileptic fit, anxiety, schizophrenia, a neurodegenerative disorder,Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis(ALS) or neonatal stress.

Finally, WO 01/72779 describes the use of an effective amount of a GRP94protein modulator for the preparation of a medicament for changing asubsequent cellular reaction to an ischaemic state in a tissue site inan individual, by treatment of the cells at the tissue site with theGRP94 protein modulator in order that the GRP94 activity in cells isincreased to such an extent that a subsequent cellular reaction to anischaemic state is changed, where the subsequent ischaemic condition ispreferably the consequence of cardiac arrest, asystolia and delayedventricular arrhythmia, heart operation, cardiopulmonary bypassoperation, organ transplant, spinal cord trauma, head trauma, stroke,thromboembolic stroke, haemorrhagic stroke, cerebral vasospasm,hypotonia, hypoglycaemia, status epilepticus, an epileptic fit, anxiety,schizophrenia, a neurodegenerative disorder, Alzheimer's disease,Huntington's disease, amyotrophic lateral sclerosis (ALS) or neonatalstress, or where the tissue site is the donor tissue for a transplant.

A. Kamal et al. in Trends in Molecular Medicine, Vol. 10 No. 6 Jun.2004, describe therapeutic and diagnostic applications of HSP90activation, inter alia for the treatment of diseases of the centralnervous system and of cardiovascular diseases.

The identification of small compounds which specifically inhibit,regulate and/or modulate HSP90 is therefore desirable and an aim of thepresent invention.

It has been found that the compounds according to the invention andsalts thereof have very valuable pharmacological properties while beingwell tolerated.

In particular, they exhibit HSP90-inhibiting properties.

The present invention therefore relates to compounds according to theinvention as medicaments and/or medicament active ingredients in thetreatment and/or prophylaxis of the said diseases and to the use ofcompounds according to the invention for the preparation of apharmaceutical for the treatment and/or prophylaxis of the said diseasesand also to a process for the treatment of the said diseases whichcomprises the administration of one or more compounds according to theinvention to a patient in need of such an administration.

The host or patient may belong to any mammalian species, for example aprimate species, particularly humans; rodents, including mice, rats andhamsters; rabbits; horses, cows, dogs, cats, etc. Animal models are ofinterest for experimental investigations, where they provide a model forthe treatment of a human disease.

PRIOR ART

WO 00/53169 describes HSP90 inhibition using coumarine or a coumarinederivative.

WO 03/041643 A2 discloses HSP90-inhibiting zearalanol derivatives.

Other HSP90-inhibiting indazole derivatives are known from WO 06/010595and WO 02/083648.

FURTHER LITERATURE

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SUMMARY OF THE INVENTION

The invention relates to compounds of the formula I

in which

-   R¹ denotes H, OH, OCH₃, OCF₃, OCHF₂, OBzl, OAc, p-methoxybenzyloxy,    SH, S(O)_(m)CH₃, SO₂NH₂, Hal, CF₃ or CH₃,-   R² denotes Alk, (CH₂)_(n)Het, CN, NO₂, NH₂, OH, OA, O(CH₂)_(n)Ar,    O(CH₂)_(n)Het, SH, COA, CO(CH₂)_(n)Ar, CO(CH₂)_(n)Het, S(O)_(m)A,    S(O)_(m)(CH₂)_(n)Ar, S(O)_(m)(CH₂)_(n)Het, NHA, NHAr, NHHet, NAA′,    COOH, COOA, CONH₂, CONHA, CONAA′, CONH(CH₂)_(n)Ar, CONA(CH₂)_(n)Ar,    CONH(CH₂)_(n)Het, CONA(CH₂)_(n)Het, SO₂NH₂, SO₂NHA, SO₂NAA′,    SO₂NH(CH₂)_(n)Ar, SO₂NA(CH₂)_(n)Ar, SO₂NH(CH₂)_(n)Het,    SO₂NA(CH₂)_(n)Het, NHCOA, NACOA′, NHCO(CH₂)_(n)Ar, NACO(CH₂)_(n)Ar,    NHCO(CH₂)_(n)Het, NACO(CH₂)_(n)Het, NHSO₂A, NASO₂A′,    NHSO₂(CH₂)_(n)Ar, NASO₂(CH₂)_(n)Ar, NHSO₂(CH₂)_(n)Het,    NASO₂(CH₂)_(n)Het, NHCOOA, NHCOOAr, NHCOOHet, NHCONHA, NHCONHAr or    NHCONHHet,-   R³ denotes H, Hal, A, AOH, COOA, CONH₂, CONHA, CONAA′, CONHAr,    CONH(CH₂)Ar, CONAAr, CONA(CH₂)Ar, CONHHet, CONH(CH₂)Het, CONAHet,    CONA(CH₂)Het, (CH₂)_(n)COOA, (CH₂)_(n)CONHA, (CH₂)_(n)CONNAA′,    (CH₂)_(n)NHCONH₂, (CH₂)_(n)NHCONHA, (CH₂)_(n)NHCONAA′,    (CH₂)_(n)NHCOA, (CH₂)_(n)NHCOAr, (CH₂)_(n)NHSO₂A, (CH₂)_(n)NHSO₂Ar,    (CH₂)_(n)NASO₂Ar, (CH₂)_(n)NHSO₂CH₂Ar, (CH₂)_(n)NASO₂CH₂Ar,    (CH₂)_(n)Ar, (CH₂)_(n)Het, NHAr or NHHet,-   Ar denotes phenyl, naphthyl or biphenyl, each of which is    unsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by A,    OA, OH, SH, S(O)_(m)A, Hal, NO₂, CN, COA, COOH, COOA, CONR⁴R⁵,    SO₂NR⁴R⁵, NR⁴R⁵, OCONR⁴R⁵, NR⁴COR⁵, NR⁴SO₂R⁵, NR⁴CONR⁴R⁵,    (CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN, SO₂Het¹, O(CH₂)_(p)NR⁴R⁵ and/or    (CH₂)_(m)Het¹,-   A, A′ each, independently of one another, denote unbranched or    branched alkyl having 1-10 C atoms, in which 1-3 CH₂ groups may be    replaced by O, S, SO, SO₂, NH, NMe or NEt and/or, in addition, 1-5H    atoms may be replaced by F and/or Cl,    -   or denote Alk or cyclic alkyl having 3-8 C atoms,-   Alk denotes alkenyl or alkynyl having 2-6 C atoms,-   Het denotes a mono- or bicyclic saturated, unsaturated or aromatic    heterocycle having 1 to 4 N, O and/or S atoms, which may be    unsubstituted or mono-, di- or trisubstituted by A, OA, OH, SH,    S(O)_(m)A, Hal, NO₂, CN, COA, COOA, CONR⁴R⁵, SONR⁴R⁵NR⁴R⁵, OCONR⁴R⁵,    NR⁴COR⁵, NR⁴SO₂R⁵, NR⁴CONR⁴R⁵, S, ═NH, ═NA and/or ═O (carbonyl    oxygen),-   Het¹ denotes a monocyclic saturated heterocycle having 1 to 3 N    and/or O atoms, which may be unsubstituted or mono-, di- or    trisubstituted by A, OA, OH and/or ═O (carbonyl oxygen),-   R⁴, R⁵ each, independently of one another, denote H or alkyl having    1-6 C atoms, in which 1-3 CH₂ groups may be replaced by O, S, SO,    SO₂, NH, NMe, or NEt and/or, in addition, 1-5H atoms may be replaced    by F and/or Cl,-   Hal denotes F, Cl, Br or I,-   m denotes 0, 1 or 2,-   n denotes 0, 1, 2, 3 or 4,-   p denotes 1, 2, 3 or 4,    and pharmaceutically usable derivatives, salts, solvates and    stereoisomers thereof including mixtures thereof in all ratios.

The invention relates to the compounds of the formula I and saltsthereof and to a process for the preparation of compounds of the formulaI and pharmaceutically usable derivatives, solvates, salts andstereoisomers thereof, characterised in that

-   a) a compound of the formula II

-   -   in which    -   R¹, R² and R³ have the meanings indicated in Claim 1,    -   and L denotes F, Cl, Br, I or a free or reactively modified OH        group,        is reacted with hydrazine or hydrazine hydrate,        one or more radical(s) R¹, R² and/or R³ are subsequently, if        desired, converted into one or more radical(s) R¹, R² and/or R³        by, for example,

-   i) reducing a nitro group to an amino group,

-   ii) hydrolysing an ester group to a carboxyl group,

-   iii) converting an amino group into an alkylated amine by reductive    amination,

-   iv) converting a carboxyl group or an ester into an amide,

-   v) acylating an amino group,    and/or    a base or acid of the formula I is converted into one of its salts.

The invention also relates to the stereoisomers (E, Z isomers) and thehydrates and solvates of these compounds. Solvates of the compounds aretaken to mean adductions of inert solvent molecules onto the compoundswhich form owing to their mutual attractive force. Solvates are, forexample, mono- or dihydrates or alcoholates.

Pharmaceutically usable derivatives are taken to mean, for example, thesalts of the compounds according to the invention and also so-calledprodrug compounds.

Prodrug derivatives are taken to mean compounds of the formula I whichhave been modified with, for example, alkyl or acyl groups, sugars oroligopeptides and which are rapidly cleaved in the organism to give theeffective compounds according to the invention.

These also include biodegradable polymer derivatives of the compoundsaccording to the invention, as described, for example, in Int. J. Pharm.115, 61-67 (1995).

The expression “effective amount” means the amount of a medicament orpharmaceutical active ingredient that causes a biological or medicalresponse which is sought or desired, for example, by a researcher orphysician in a tissue, system, animal or human.

In addition, the expression “therapeutically effective amount” means anamount which, compared with a corresponding subject who has not receivedthis amount, has the following consequence:

improved healing treatment, healing, prevention or elimination of adisease, a disease picture, a condition, a complaint, a disorder or ofside effects or also the reduction in the progress of a disease, acomplaint or a disorder.

The term “therapeutically effective amount” also encompasses the amountswhich are effective for increasing normal physiological function.

The invention also relates to mixtures of the compounds of the formula Iaccording to the invention, for example mixtures of two diastereomers,for example in the ratio 1:1, 1:2, 1:3, 1:4, 1:5, 1:10, 1:100 or 1:1000.

These are particularly preferably mixtures of stereoisomeric compounds.

For all radicals which occur more than once, their meanings areindependent of one another.

Above and below, the radicals and parameters R¹, R² and R³ have themeanings indicated for the formula I, unless expressly indicatedotherwise.

A or A′ preferably denotes alkyl, is unbranched (linear) or branched,and has 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms. A or A′ particularlypreferably denotes methyl, ethyl, propyl, isopropyl, butyl, isobutyl,sec-butyl or tert-butyl, furthermore also pentyl, 1-, 2- or3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl,1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methylpropyl,1-ethyl-2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl.

A or A′ very particularly preferably denotes alkyl having 1, 2, 3, 4, 5or 6 C atoms, preferably ethyl, propyl, isopropyl, butyl, isobutyl,sec-butyl, tert-butyl, pentyl, hexyl, trifluoromethyl, pentafluoroethylor 1,1,1-trifluoroethyl. A, A′ also each denote, independently of oneanother, unbranched or branched alkyl having 1-10 C atoms, in which 1-3CH₂ groups may be replaced by O, S, SO, SO₂, NH, NMe, or NEt, such as,for example, 2-methoxyethyl or 3-methylaminopropyl.

A or A′ also denotes cyclic alkyl (cycloalkyl). Cycloalkyl preferablydenotes cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl or cycloheptyl.Cyclic alkyl furthermore preferably denotes cyclopropylmethyl,cyclopentylmethyl or cyclohexylmethyl.

A or A′ also denotes Alk. Alk denotes alkenyl having 2-6 C atoms, suchas, for example, vinyl or propenyl. Alk also denotes alkynyl, such as,for example, ethynyl.

R¹ preferably denotes OH, OCH₃ or SH, particularly preferably OH orOCH₃, furthermore also OCF₃, OCHF₂.

R² preferably denotes CONH₂, CONHA, CONAA′, CONH(CH₂)_(n)Ar,CONA(CH₂)_(n)Ar, CONH(CH₂)_(n)Het or CONA(CH₂)_(n)Het,

where A, A′ denotes alkyl having 1, 2, 3 or 4 C atoms or cyclic alkylhaving 3-8 C atoms.

R³ preferably denotes A or (CH₂)_(n)Ar,

where Ar denotes phenyl which is unsubstituted or mono-, di- ortrisubstituted by A, Hal and/or OA.

R⁴ or R⁵ preferably denotes alkyl, is unbranched (linear) or branched,and has 1, 2, 3, 4, 5, 6, 7, 8, 9 or 10 C atoms. R⁴ or R⁵ particularlypreferably denotes methyl, ethyl, propyl, isopropyl, butyl, isobutyl,sec-butyl or tert-butyl, furthermore also pentyl, 1-, 2- or3-methylbutyl, 1,1-, 1,2- or 2,2-dimethylpropyl, 1-ethylpropyl, hexyl,1-, 2-, 3- or 4-methylpentyl, 1,1-, 1,2-, 1,3-, 2,2-, 2,3- or3,3-dimethylbutyl, 1- or 2-ethylbutyl, 1-ethyl-1-methyl propyl,1-ethyl-2-methylpropyl, 1,1,2- or 1,2,2-trimethylpropyl.

R⁴ or R⁵ particularly preferably denotes alkyl having 1, 2, 3, 4, 5 or 6C atoms, preferably ethyl, propyl, isopropyl, butyl, isobutyl,sec-butyl, tert-butyl, pentyl, hexyl, trifluoromethyl, pentafluoroethylor 1,1,1-trifluoroethyl, R⁴, R⁵ also each denote, independently of oneanother, unbranched or branched alkyl having 1-6 C atoms, in which 1-3CH₂ groups may be replaced by O, S, SO, SO₂, NH, NMe, or NEt, such as,for example, 2-methoxyethyl or 3-methylaminopropyl.

n preferably denotes 0 or 1.

Ar denotes, for example, phenyl, o-, m- or p-tolyl, o-, m- orp-ethylphenyl, o-, m- or p-propylphenyl, o-, m- or p-isopropylphenyl,o-, m- or p-tert-butylphenyl, o-, m- or p-hydroxyphenyl, o-, m- orp-nitrophenyl, o-, m- or p-aminophenyl, o-, m- orp-(N-methylamino)phenyl, o-, m- or p-(N-methylaminocarbonyl)phenyl, o-,m- or p-acetamidophenyl, o-, m- or p-methoxyphenyl, o-, m- orp-ethoxyphenyl, o-, m- or p-ethoxycarbonylphenyl, o-, m- orp-(N,N-dimethylamino)phenyl, o-, m- orp-(N,N-dimethylaminocarbonyl)phenyl, o-, m- or p-(N-ethylamino)phenyl,o-, m- or p-(N,N-diethylamino)phenyl, o-, m- or p-fluorophenyl, o-, m-or p-bromophenyl, o-, m- or p-chlorophenyl, o-, m- orp-(methylsulfonamido)phenyl, o-, m- or p-(methylsulfonyl)phenyl, o-, m-or p-cyanophenyl, o-, m- or p-ureidophenyl, o-, m- or p-formylphenyl,o-, m- or p-acetylphenyl, o-, m- or p-aminosulfonylphenyl, o-, m- orp-carboxyphenyl, o, m- or p-carboxymethylphenyl, o-, m- orp-carboxymethoxyphenyl, further preferably 2,3-, 2,4-, 2,5-, 2,6-, 3,4-or 3,5-difluorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or3,5-dichlorophenyl, 2,3-, 2,4-, 2,5-, 2,6-, 3,4- or 3,5-dibromophenyl,2,4- or 2,5-dinitrophenyl, 2,5- or 3,4-dimethoxyphenyl,3-nitro-4-chlorophenyl, 3-amino-4-chloro-, 2-amino-3-chloro-,2-amino-4-chloro-, 2-amino-5-chloro- or 2-amino-6-chlorophenyl,2-nitro-4-N,N-dimethylamino- or 3-nitro-4-N,N-dimethylaminophenyl,2,3-diaminophenyl, 2,3,4-, 2,3,5-, 2,3,6-, 2,4,6- or3,4,5-trichlorophenyl, 2,4,6-trimethoxyphenyl,2-hydroxy-3,5-dichlorophenyl, p-iodophenyl, 3,6-dichloro-4-aminophenyl,4-fluoro-3-chlorophenyl, 2-fluoro-4-bromophenyl,2,5-difluoro-4-bromophenyl, 3-bromo-6-methoxyphenyl,3-chloro-6-methoxyphenyl, 3-chloro-4-acetamidophenyl,3-fluoro-4-methoxyphenyl, 3-amino-6-methylphenyl,3-chloro-4-acetamidophenyl or 2,5-dimethyl-4-chlorophenyl.

Ar preferably denotes phenyl which is unsubstituted or mono-, di-, tri-,tetra- or pentasubstituted by A, OA, OH, CN, NH₂, NHA, NA₂, NHCOA, Hal,CONH₂, CONHA, CONAA′, (CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN, SO₂Het¹,O(CH₂)_(p)NH₂, O(CH₂)_(p)NA₂, O(CH₂)_(p)NHA and/or (CH₂)_(m)Het¹.

Irrespective of further substitutions, Het denotes, for example, 2- or3-furyl, 2- or 3-thienyl, 1-, 2- or 3-pyrrolyl, 1-, 2,4- or5-imidazolyl, 1-, 3-, 4- or 5-pyrazolyl, 2-, 4- or 5-oxazolyl, 3-, 4- or5-isoxazolyl, 2-, 4- or 5-thiazolyl, 3-, 4- or 5-isothiazolyl, 2-, 3- or4-pyridyl, 2-, 4-, 5- or 6-pyrimidinyl, furthermore preferably1,2,3-triazol-1-, -4- or -5-yl, 1,2,4-triazol-1-, -3- or 5-yl, 1- or5-tetrazolyl, 1,2,3-oxadiazol-4- or -5-yl, 1,2,4-oxadiazol-3- or -5-yl,1,3,4-thiadiazol-2- or -5-yl, 1,2,4-thiadiazol-3- or -5-yl,1,2,3-thiadiazol-4- or -5-yl, 3- or 4-pyridazinyl, pyrazinyl, 1-, 2-,3-, 4-, 5-, 6- or 7-indolyl, 4- or 5-isoindolyl, 1-, 2-, 4- or5-benzimidazolyl, 1-, 2-, 3-, 4-, 5-, 6- or 7-indazolyl, 1-, 3-, 4-, 5-,6- or 7-benzopyrazolyl, 2-, 4-, 5-, 6- or 7-benzoxazolyl, 3-, 4-, 5-, 6-or 7-benzisoxazolyl, 2-, 4-, 5-, 6- or 7-benzothiazolyl, 2-, 4-, 5-, 6-or 7-benzisothiazolyl, 4-, 5-, 6- or 7-benzoxadiazolyl, 2-, 3-, 4-, 5-,6-, 7- or 8-quinolyl, 1-, 3-, 4-, 5-, 6-, 7- or 8-isoquinolyl, 3-, 4-,5-, 6-, 7- or 8-cinnolinyl, 2-, 4-, 5-, 6-, 7- or 8-quinazolinyl, 5- or6-quinoxalinyl, 2-, 3-, 5-, 6-, 7- or 8-2H-benzo-1,4-oxazinyl, furtherpreferably 1,3-benzodioxol-5-yl, 1,4-benzodioxan-6-yl,2,1,3-benzothiadiazol-4- or -5-yl or 2,1,3-benzoxadiazol-5-yl.

The heterocyclic radicals may also be partially or fully hydrogenated.Het can thus also denote, for example, 2,3-dihydro-2-, -3-, -4- or-5-furyl, 2,5-dihydro-2-, -3-, -4- or 5-furyl, tetrahydro-2- or-3-furyl, 1,3-dioxolan-4-yl, tetrahydro-2- or -3-thienyl,2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrrolyl, 2,5-dihydro-1-, -2-, -3-,-4- or -5-pyrrolyl, 1-, 2- or 3-pyrrolidinyl, tetrahydro-1-, -2- or-4-imidazolyl, 2,3-dihydro-1-, -2-, -3-, -4- or -5-pyrazolyl,tetrahydro-1-, -3- or -4-pyrazolyl, 1,4-dihydro-1-, -2-, -3- or-4-pyridyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5- or -6-pyridyl, 1-,2-, 3- or 4-piperidinyl, 2-, 3- or 4-morpholinyl, tetrahydro-2-, -3- or-4-pyranyl, 1,4-dioxanyl, 1,3-dioxan-2-, -4- or -5-yl, hexahydro-1-, -3-or -4-pyridazinyl, hexahydro-1-, -2-, -4- or -5-pyrimidinyl, 1-, 2- or3-piperazinyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or-8-quinolyl, 1,2,3,4-tetrahydro-1-, -2-, -3-, -4-, -5-, -6-, -7- or-8-isoquinolyl, 2-, 3-, 5-, 6-, 7- or 8-3,4-dihydro-2H-benzo-1,4-oxazinyl, further preferably2,3-methylenedioxyphenyl, 3,4-methylenedioxyphenyl,2,3-ethylenedioxyphenyl, 3,4-ethylenedioxyphenyl,3,4-(difluoromethylenedioxy)phenyl, 2,3-dihydrobenzofuran-5- or 6-yl,2,3-(2-oxomethylenedioxy)phenyl or also3,4-dihydro-2H-1,5-benzodioxepin-6- or -7-yl, furthermore preferably2,3-dihydrobenzofuranyl or 2,3-dihydro-2-oxofuranyl.

Het preferably denotes a mono- or bicyclic saturated, unsaturated oraromatic heterocycle having 1 to 3 N, O and/or S atoms, which may beun-substituted or mono-, di- or trisubstituted by A, Hal, COA, OH, OA,—NH, ═NA and/or ═O (carbonyl oxygen). Het particularly preferablydenotes pyridyl, furyl, thienyl, pyrrolyl, oxazolyl, isoxazolyl,imidazolyl, pyrimidinyl, pyrazolyl, thiazolyl, pyrazinyl, pyridazinyl,pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl, benzodioxanyl,benzodioxolyl, indolyl, quinolinyl, benzimidazolyl, benzothiadiazolyl,indazolyl, dihydrobenzimidazolyl, dihydroindolyl or tetrahydropyranyl,each of which is unsubstituted or mono-, di- or trisubstituted by A,Hal, OH, OA, COA and/or ═O (carbonyl oxygen).

Het¹ denotes a monocyclic saturated heterocycle having 1 to 3 N and/or Oatoms, which may be unsubstituted or mono-, di- or trisubstituted by A,OA, OH and/or ═O (carbonyl oxygen), preferably morpholinyl, piperazinylor 1,3-oxazinanyl, each of which may be mono- or disubstituted by Aand/or ═O (carbonyl oxygen).

The compounds of the formula I may have one or more chiral centres andtherefore occur in various stereoisomeric forms. The formula Iencompasses all these forms.

Accordingly, the invention relates, in particular, to the compounds ofthe formula I in which at least one of the said radicals has one of thepreferred meanings indicated above. Some preferred groups of compoundsmay be expressed by the following sub-formulae Ia to Ii, which conformto the formula I and in which the radicals not designated in greaterdetail have the meaning indicated for the formula I, but in which

-   in Ia R¹ denotes OH or OCH₃;-   in Ib R² denotes CONH₂, CONHA, CONAA′, CONH(CH₂)_(n)Ar,    CONA(CH₂)_(n)Ar, CONH(CH₂)_(n)Het or CONA(CH₂)_(n)Het, where A, A′    denotes alkyl having 1, 2, 3 or 4 C atoms or cyclic alkyl having 3-8    C atoms;-   in Ic R³ denotes A or (CH₂)_(n)Ar,    -   where Ar denotes phenyl which is unsubstituted or mono-, di- or        trisubstituted by A, Hal and/or OA;-   in Id Ar denotes phenyl which is unsubstituted or mono-, di-, tri-,    tetra- or pentasubstituted by A, OA, OH, CN, NH₂, NHA, NA₂, NHCOA,    Hal, CONH₂, CONHA, CONAA′, (CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN, SO₂Het¹,    O(CH₂)_(p)NH₂, O(CH₂)_(p)NA₂, O(CH₂)_(p)NHA and/or (CH₂)_(m)Het¹;-   in Ie A, A′ each, independently of one another, denote unbranched or    branched alkyl having 1-6 C atoms, in which 1 or 2 CH₂ groups may be    replaced by O, NH, NMe or NEt and/or, in addition, 1-5H atoms may be    replaced by F and/or Cl,    -   or denote cyclic alkyl having 3-8 C atoms;-   in If A, A′ each, independently of one another, denote unbranched or    branched alkyl having 1-6 C atoms, in which 1 CH₂ group may be    replaced by O and/or, in addition, 1-5H atoms may be replaced by F    and/or Cl,    -   or denote cyclic alkyl having 3-8 C atoms;-   in Ig Het denotes a mono- or bicyclic saturated, unsaturated or    aromatic heterocycle having 1 to 3 N, O and/or S atoms, which may be    unsubstituted or mono-, di- or trisubstituted by A, Hal, OH, OA,    COA, ═NH, ═NA and/or ═O (carbonyl oxygen);

in Ih Het denotes pyridyl, furyl, thienyl, pyrrolyl, oxazolyl,isoxazolyl, imidazolyl, pyrimidinyl, pyrazolyl, thiazolyl, pyrazinyl,pyridazinyl, pyrrolidinyl, piperidinyl, morpholinyl, piperazinyl,benzodioxanyl, benzodioxolyl, indolyl, quinolinyl, benzimidazolyl,benzothiadiazolyl, indazolyl, dihydrobenzimidazolyl, dihydroindolyl ortetrahydropyranyl, each of which is unsubstituted or mono-, di- ortrisubstituted by A, Hal, OH, OA, COA and/or ═O (carbonyl oxygen);

-   in Ii R¹ denotes OH or OCH₃,    -   R² denotes CONH₂, CONHA, CONAA′, CONH(CH₂)_(n)Ar,        CONA(CH₂)_(n)Ar, CONH(CH₂)_(n)Het or CONA(CH₂)_(n)Het, where A,        A′ denotes alkyl having 1, 2, 3 or 4 C atoms or cyclic alkyl        having 3-8 C atoms,    -   R³ denotes A or (CH₂)_(n)Ar,        -   where Ar denotes phenyl which is unsubstituted or mono-, di-            or trisubstituted by A, Hal and/or OA,    -   Ar denotes phenyl which is unsubstituted or mono-, di-, tri-,        tetra- or pentasubstituted by A, OA, OH, CN, NH₂, NHA, NA₂,        NHCOA, Hal, CONH₂, CONHA, CONAA′, (CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN,        SO₂Het¹, O(CH₂)_(p)NH₂, O(CH₂)_(p)NA₂, O(CH₂)_(p)NHA and/or        (CH₂)_(m)Het¹,    -   A, A′ each, independently of one another, denote unbranched or        branched alkyl having 1-6 C atoms, in which 1 CH₂ group may be        replaced by O and/or, in addition, 1-5H atoms may be replaced by        F and/or Cl,        -   or denote cyclic alkyl having 3-8 C atoms;            and pharmaceutically usable derivatives, solvates, salts and            stereoisomers thereof, including mixtures thereof in all            ratios.

The compounds according to the invention and also the starting materialsfor their preparation are, in addition, prepared by methods known perse, as described in the literature (for example in the standard works,such as Houben-Weyl, Methoden der organischen Chemie [Methods of OrganicChemistry], Georg-Thieme-Verlag, Stuttgart), to be precise underreaction conditions which are known and suitable for the said reactions.Use may also be made here of variants known per se which are notmentioned here in greater detail.

If desired, the starting materials can also be formed in situ by notisolating them from the reaction mixture, but instead immediatelyconverting them further into the compounds according to the invention.

The starting compounds are generally known. If they are novel, however,they can be prepared by methods known per se.

Compounds of the formula I can preferably be obtained by reacting acompound of the formula II with hydrazine or hydrazine hydrate. In thecompounds of the formula II, L preferably denotes F, Cl, Br, I or a freeor reactively modified OH group, such as, for example, an activatedester, an imidazolide or alkylsulfonyloxy having 1-6 C atoms (preferablymethylsulfonyloxy or trifluoromethylsulfonyloxy) or arylsulfonyloxyhaving 6-10 C atoms (preferably phenyl- or p-tolylsulfonyloxy). In thecompounds of the formula II, L preferably denotes F.

The reaction is carried out by methods which are known to the personskilled in the art.

The reaction is initially carried out in a suitable solvent.

Examples of suitable solvents are hydrocarbons, such as hexane,petroleum ether, benzene, toluene or xylene; chlorinated hydrocarbons,such as trichloroethylene, 1,2-dichloroethane, carbon tetrachloride,chloroform or dichloromethane; alcohols, such as methanol, ethanol,isopropanol, n-propanol, n-butanol or tert-butanol; ethers, such asdiethyl ether, diisopropyl ether, tetrahydrofuran (THF) or dioxane;glycol ethers, such as ethylene glycol monomethyl or monoethyl ether,ethylene glycol dimethyl ether (diglyme); ketones, such as acetone orbutanone; amides, such as acetamide, dimethylacetamide ordimethylformamide (DMF); nitrites, such as acetonitrile; sulfoxides,such as dimethyl sulfoxide (DMSO); carbon disulfide; carboxylic acids,such as formic acid or acetic acid; nitro compounds, such asnitromethane or nitrobenzene; esters, such as ethyl acetate, or mixturesof the said solvents.

The solvent is particularly preferably 1,4-dioxane or n-butanol.

Depending on the conditions used, the reaction time is between a fewminutes and 14 days, the reaction temperature is between about 0° and150°, normally between 15° and 120°, particularly preferably between 50and 100° C.

If desired, one or more radical(s) R¹, R² and/or R³ in the resultantcompounds is subsequently converted into one or more radical(s) R¹, R²and/or R³

by, for example, reducing nitro groups to amino groups, for example byhydrogenation on Raney nickel or Pd/carbon in an inert solvent, such asmethanol or ethanol,or hydrolysing an ester group to a carboxyl group,or converting an amino group into an alkylated amine by reductiveamination,or converting a carboxyl group or an ester into an amide.

Furthermore, free amino groups can be acylated in a conventional mannerusing an acid chloride or anhydride or alkylated using an unsubstitutedor substituted alkyl halide, advantageously in an inert solvent, such asdichloromethane or THF, and/or in the presence of a base, such astriethylamine or pyridine, at temperatures between −60° and +30°.

Pharmaceutical Salts and Other Forms

The said compounds according to the invention can be used in their finalnon-salt form. On the other hand, the present invention also encompassesthe use of these compounds in the form of their pharmaceuticallyacceptable salts, which can be derived from various organic andinorganic acids and bases by procedures known in the art.Pharmaceutically acceptable salt forms of the compounds according to theinvention are for the most part prepared by conventional methods. If thecompound according to the invention contains a carboxyl group, one ofits suitable salts can be formed by reacting the compound with asuitable base to give the corresponding base-addition salt. Such basesare, for example, alkali metal hydroxides, including potassiumhydroxide, sodium hydroxide and lithium hydroxide; alkaline-earth metalhydroxides, such as barium hydroxide and calcium hydroxide; alkali metalalkoxides, for example potassium ethoxide and sodium propoxide; andvarious organic bases, such as piperidine, diethanolamine andN-methylglutamine. The aluminium salts of the compounds of the formula Iare likewise included. In the case of certain compounds of the formulaI, acid-addition salts can be formed by treating these compounds withpharmaceutically acceptable organic and inorganic acids, for examplehydrogen halides, such as hydrogen chloride, hydrogen bromide orhydrogen iodide, other mineral acids and corresponding salts thereof,such as sulfate, nitrate or phosphate and the like, and alkyl- andmonoarylsulfonates, such as ethanesulfonate, toluenesulfonate andbenzenesulfonate, and other organic acids and corresponding saltsthereof, such as acetate, trifluoroacetate, tartrate, maleate,succinate, citrate, benzoate, salicylate, ascorbate and the like.Accordingly, pharmaceutically acceptable acid-addition salts of thecompounds of the formula I include the following: acetate, adipate,alginate, arginate, aspartate, benzoate, benzenesulfonate (besylate),bisulfate, bisulfite, bromide, butyrate, camphorate, camphorsulfonate,caprylate, chloride, chlorobenzoate, citrate, cyclopentanepropionate,digluconate, dihydrogenphosphate, dinitrobenzoate, dodecylsulfate,ethanesulfonate, fumarate, galacterate (from mucic acid), galacturonate,glucoheptanoate, gluconate, glutamate, glycerophosphate, hemisuccinate,hemisulfate, heptanoate, hexanoate, hippurate, hydrochloride,hydrobromide, hydroiodide, 2-hydroxyethanesulfonate, iodide,isethionate, isobutyrate, lactate, lactobionate, malate, maleate,malonate, mandelate, metaphosphate, methanesulfonate, methylbenzoate,monohydrogenphosphate, 2-naphthalenesulfonate, nicotinate, nitrate,oxalate, oleate, palmoate, pectinate, persulfate, phenylacetate,3-phenylpropionate, phosphate, phosphonate, phthalate, but this does notrepresent a restriction.

Furthermore, the base salts of the compounds according to the inventioninclude aluminium, ammonium, calcium, copper, iron(III), iron(II),lithium, magnesium, manganese(III), manganese(II), potassium, sodium andzinc salts, but this is not intended to represent a restriction. Of theabove-mentioned salts, preference is given to ammonium; the alkali metalsalts sodium and potassium, and the alkaline-earth metal salts calciumand magnesium. Salts of the compounds according to the invention whichare derived from pharmaceutically acceptable organic non-toxic basesinclude salts of primary, secondary and tertiary amines, substitutedamines, also including naturally occurring substituted amines, cyclicamines, and basic ion exchanger resins, for example arginine, betaine,caffeine, chloroprocaine, choline, N,N′-dibenzylethylenediamine(benzathine), dicyclohexylamine, diethanolamine, diethylamine,2-diethylaminoethanol, 2-dimethylaminoethanol, ethanolamine,ethylenediamine, N-ethylmorpholine, N-ethylpiperidine, glucamine,glucosamine, histidine, hydrabamine, isopropylamine, lidocaine, lysine,meglumine, N-methyl-D-glucamine, morpholine, piperazine, piperidine,polyamine resins, procaine, purines, theobromine, triethanolamine,triethylamine, trimethylamine, tripropylamine andtris(hydroxymethyl)methylamine (tromethamine), but this is not intendedto represent a restriction.

Compounds of the present invention which contain basicnitrogen-containing groups can be quaternised using agents such as(C₁-C₄)alkyl halides, for example methyl, ethyl, isopropyl andtert-butyl chloride, bromide and iodide; di(C₁-C₄)alkyl sulfates, forexample dimethyl, diethyl and diamyl sulfate; (C₁₀-C₁₈)alkyl halides,for example decyl, dodecyl, lauryl, myristyl and stearyl chloride,bromide and iodide; and aryl(C₁-C₄)alkyl halides, for example benzylchloride and phenethyl bromide. Both water- and oil-soluble compoundsaccording to the invention can be prepared using such salts.

The above-mentioned pharmaceutical salts which are preferred includeacetate, trifluoroacetate, besylate, citrate, fumarate, gluconate,hemisuccinate, hippurate, hydrochloride, hydrobromide, isethionate,mandelate, meglumine, nitrate, oleate, phosphonate, pivalate, sodiumphosphate, stearate, sulfate, sulfosalicylate, tartrate, thiomalate,tosylate and tromethamine, but this is not intended to represent arestriction.

The acid-addition salts of basic compounds according to the inventionare prepared by bringing the free base form into contact with asufficient amount of the desired acid, causing the formation of the saltin a conventional manner. The free base can be regenerated by bringingthe salt form into contact with a base and isolating the free base in aconventional manner. The free base forms differ in a certain respectfrom the corresponding salt forms thereof with respect to certainphysical properties, such as solubility in polar solvents; for thepurposes of the invention, however, the salts otherwise correspond tothe respective free base forms thereof.

As mentioned, the pharmaceutically acceptable base-addition salts of thecompounds according to the invention are formed with metals or amines,such as alkali metals and alkaline-earth metals or organic amines.Preferred metals are sodium, potassium, magnesium and calcium. Preferredorganic amines are N,N′-dibenzylethylenediamine, chloroprocaine,choline, diethanolamine, ethylenediamine, N-methyl-D-glucamine andprocaine.

The base-addition salts of acidic compounds according to the inventionare prepared by bringing the free acid form into contact with asufficient amount of the desired base, causing the formation of the saltin a conventional manner. The free acid can be regenerated by bringingthe salt form into contact with an acid and isolating the free acid in aconventional manner. The free acid forms differ in a certain respectfrom the corresponding salt forms thereof with respect to certainphysical properties, such as solubility in polar solvents; for thepurposes of the invention, however, the salts otherwise correspond tothe respective free acid forms thereof.

If a compound according to the invention contains more than one groupwhich is capable of forming pharmaceutically acceptable salts of thistype, the invention also encompasses multiple salts. Typical multiplesalt forms include, for example, bitartrate, diacetate, difumarate,dimeglumine, diphosphate, disodium and trihydrochloride, but this is notintended to represent a restriction.

With regard to that stated above, it can be seen that the expression“pharmaceutically acceptable salt” in the present connection is taken tomean an active ingredient which comprises a compound according to theinvention in the form of one of its salts, in particular if this saltform imparts improved pharmacokinetic properties on the activeingredient compared with the free form of the active ingredient or anyother salt form of the active ingredient used earlier. Thepharmaceutically acceptable salt form of the active ingredient can alsoprovide this active ingredient for the first time with a desiredpharmacokinetic property which it did not have earlier and can even havea positive influence on the pharmacodynamics of this active ingredientwith respect to its therapeutic efficacy in the body.

Compounds according to the invention may be chiral owing to theirmolecular structure and may accordingly occur in various enantiomericforms. They can therefore exist in racemic or in optically active form.

Since the pharmaceutical activity of the racemates or stereoisomers ofthe compounds according to the invention may differ, it may be desirableto use the enantiomers. In these cases, the end product or even theintermediates can be separated into enantiomeric compounds by chemicalor physical measures known to the person skilled in the art or evenemployed as such in the synthesis.

In the case of racemic amines, diastereomers are formed from the mixtureby reaction with an optically active resolving agent. Examples ofsuitable resolving agents are optically active acids, such as the R andS forms of tartaric acid, diacetyltartaric acid, dibenzoyltartaric acid,mandelic acid, malic acid, lactic acid, suitably N-protected amino acids(for example N-benzoylproline or N-benzenesulfonylproline), or thevarious optically active camphorsulfonic acids. Also advantageous ischromatographic enantiomer resolution with the aid of an opticallyactive resolving agent (for example dinitrobenzoylphenylglycine,cellulose triacetate or other derivatives of carbohydrates or chirallyderivatised methacrylate polymers immobilised on silica gel). Suitableeluents for this purpose are aqueous or alcoholic solvent mixtures, suchas, for example, hexane/isopropanol/acetonitrile, for example in theratio 82:15:3.

The invention furthermore relates to the use of the compounds and/orphysiologically acceptable salts thereof for the preparation of amedicament (pharmaceutical composition), in particular by non-chemicalmethods. They can be converted into a suitable dosage form here togetherwith at least one solid, liquid and/or semi-liquid excipient or adjuvantand, if desired, in combination with one or more further activeingredients.

The invention furthermore relates to medicaments comprising at least onecompound according to the invention and/or pharmaceutically usablederivatives, solvates and stereoisomers thereof including mixturesthereof in all ratios, and optionally excipients and/or adjuvants.

Pharmaceutical formulations can be administered in the form of dosageunits which comprise a predetermined amount of active ingredient perdosage unit. Such a unit can comprise, for example, 0.1 mg to 3 g,preferably 1 mg to 700 mg, particularly preferably 5 mg to 100 mg, of acompound according to the invention, depending on the condition treated,the method of administration and the age, weight and condition of thepatient, or pharmaceutical formulations can be administered in the formof dosage units which comprise a predetermined amount of activeingredient per dosage unit. Preferred dosage unit formulations are thosewhich comprise a daily dose or part-dose, as indicated above, or acorresponding fraction thereof of an active ingredient. Furthermore,pharmaceutical formulations of this type can be prepared using a processwhich is generally known in the pharmaceutical art.

Pharmaceutical formulations can be adapted for administration via anydesired suitable method, for example by oral (including buccal orsublingual), rectal, nasal, topical (including buccal, sublingual ortransdermal), vaginal or parenteral (including subcutaneous,intramuscular, intravenous or intradermal) methods. Such formulationscan be prepared using all processes known in the pharmaceutical art by,for example, combining the active ingredient with the excipient(s) oradjuvant(s).

Pharmaceutical formulations adapted for oral administration can beadministered as separate units, such as, for example, capsules ortablets; powders or granules; solutions or suspensions in aqueous ornon-aqueous liquids; edible foams or foam foods; or oil-in-water liquidemulsions or water-in-oil liquid emulsions.

Thus, for example, in the case of oral administration in the form of atablet or capsule, the active-ingredient component can be combined withan oral, non-toxic and pharmaceutically acceptable inert excipient, suchas, for example, ethanol, glycerol, water and the like. Powders areprepared by comminuting the compound to a suitable fine size and mixingit with a pharmaceutical excipient comminuted in a similar manner, suchas, for example, an edible carbohydrate, such as, for example, starch ormannitol. A flavour, preservative, dispersant and dye may likewise bepresent.

Capsules are produced by preparing a powder mixture as described aboveand filling shaped gelatine shells therewith. Glidants and lubricants,such as, for example, highly disperse silicic acid, talc, magnesiumstearate, calcium stearate or polyethylene glycol in solid form, can beadded to the powder mixture before the filling operation. A disintegrantor solubiliser, such as, for example, agar-agar, calcium carbonate orsodium carbonate, may likewise be added in order to improve theavailability of the medicament after the capsule has been taken.

In addition, if desired or necessary, suitable binders, lubricants anddisintegrants as well as dyes can likewise be incorporated into themixture. Suitable binders include starch, gelatine, natural sugars, suchas, for example, glucose or beta-lactose, sweeteners made from maize,natural and synthetic rubber, such as, for example, acacia, tragacanthor sodium alginate, carboxymethylcellulose, polyethylene glycol, waxes,and the like. The lubricants used in these dosage forms include sodiumoleate, sodium stearate, magnesium stearate, sodium benzoate, sodiumacetate, sodium chloride and the like. The disintegrants include,without being restricted thereto, starch, methylcellulose, agar,bentonite, xanthan gum and the like. The tablets are formulated by, forexample, preparing a powder mixture, granulating or dry-pressing themixture, adding a lubricant and a disintegrant and pressing the entiremixture to give tablets. A powder mixture is prepared by mixing thecompound comminuted in a suitable manner with a diluent or a base, asdescribed above, and optionally with a binder, such as, for example,carboxymethylcellulose, an alginate, gelatine or polyvinylpyrrolidone, adissolution retardant, such as, for example, paraffin, an absorptionaccelerator, such as, for example, a quaternary salt, and/or anabsorbent, such as, for example, bentonite, kaolin or dicalciumphosphate. The powder mixture can be granulated by wetting it with abinder, such as, for example, syrup, starch paste, acadia mucilage orsolutions of cellulose or polymer materials and pressing it through asieve. As an alternative to granulation, the powder mixture can be runthrough a tabletting machine, giving lumps of non-uniform shape whichare broken up to form granules. The granules can be lubricated byaddition of stearic acid, a stearate salt, talc or mineral oil in orderto prevent sticking to the tablet casting moulds. The lubricated mixtureis then pressed to give tablets. The compounds according to theinvention can also be combined with a free-flowing inert excipient andthen pressed directly to give tablets without carrying out thegranulation or dry-pressing steps. A transparent or opaque protectivelayer consisting of a shellac sealing layer, a layer of sugar or polymermaterial and a gloss layer of wax may be present. Dyes can be added tothese coatings in order to be able to differentiate between differentdosage units.

Oral liquids, such as, for example, solution, syrups and elixirs, can beprepared in the form of dosage units so that a given quantity comprisesa pre-specified amount of the compound. Syrups can be prepared bydissolving the compound in an aqueous solution with a suitable flavour,while elixirs are prepared using a non-toxic alcoholic vehicle.Suspensions can be formulated by dispersion of the compound in anon-toxic vehicle. Solubilisers and emulsifiers, such as, for example,ethoxylated isostearyl alcohols and polyoxyethylene sorbitol ethers,preservatives, flavour additives, such as, for example, peppermint oilor natural sweeteners or saccharin, or other artificial sweeteners andthe like, can likewise be added.

The dosage unit formulations for oral administration can, if desired, beencapsulated in microcapsules. The formulation can also be prepared insuch a way that the release is extended or retarded, such as, forexample, by coating or embedding of particulate material in polymers,wax and the like.

The compounds according to the invention and salts, solvates andphysiologically functional derivatives thereof can also be administeredin the form of liposome delivery systems, such as, for example, smallunilamellar vesicles, large unilamellar vesicles and multilamellarvesicles. Liposomes can be formed from various phospholipids, such as,for example, cholesterol, stearylamine or phosphatidylcholines.

The compounds according to the invention and the salts, solvates andphysiologically functional derivatives thereof can also be deliveredusing monoclonal antibodies as individual carriers to which the compoundmolecules are coupled. The compounds can also be coupled to solublepolymers as targeted medicament carriers. Such polymers may encompasspolyvinylpyrrolidone, pyran copolymer,polyhydroxypropylmethacrylamidophenol, polyhydroxyethylaspartamidophenolor polyethylene oxide polylysine, substituted by palmitoyl radicals. Thecompounds may furthermore be coupled to a class of biodegradablepolymers which are suitable for achieving controlled release of amedicament, for example polylactic acid, poly-epsilon-caprolactone,polyhydroxybutyric acid, polyorthoesters, polyacetals,polydihydroxypyrans, polycyanoacrylates and crosslinked or amphipathicblock copolymers of hydrogels.

Pharmaceutical formulations adapted for transdermal administration canbe administered as independent plasters for extended, close contact withthe epidermis of the recipient. Thus, for example, the active ingredientcan be delivered from the plaster by iontophoresis, as described ingeneral terms in Pharmaceutical Research, 3(6), 318 (1986).

Pharmaceutical compounds adapted for topical administration can beformulated as ointments, creams, suspensions, lotions, powders,solutions, pastes, gels, sprays, aerosols or oils.

For the treatment of the eye or other external tissue, for example mouthand skin, the formulations are preferably applied as topical ointment orcream. In the case of formulation to give an ointment, the activeingredient can be employed either with a paraffinic or a water-misciblecream base. Alternatively, the active ingredient can be formulated togive a cream with an oil-in-water cream base or a water-in-oil base.

Pharmaceutical formulations adapted for topical application to the eyeinclude eye drops, in which the active ingredient is dissolved orsuspended in a suitable carrier, in particular an aqueous solvent.

Pharmaceutical formulations adapted for topical application in the mouthencompass lozenges, pastilles and mouthwashes.

Pharmaceutical formulations adapted for rectal administration can beadministered in the form of suppositories or enemas.

Pharmaceutical formulations adapted for nasal administration in whichthe carrier substance is a solid comprise a coarse powder having aparticle size, for example, in the range 20-500 microns, which isadministered in the manner in which snuff is taken, i.e. by rapidinhalation via the nasal passages from a container containing the powderheld close to the nose. Suitable formulations for administration asnasal spray or nose drops with a liquid as carrier substance encompassactive-ingredient solutions in water or oil.

Pharmaceutical formulations adapted for administration by inhalationencompass finely particulate dusts or mists, which can be generated byvarious types of pressurised dispensers with aerosols, nebulisers orinsufflators.

Pharmaceutical formulations adapted for vaginal administration can beadministered as pessaries, tampons, creams, gels, pastes, foams or sprayformulations.

Pharmaceutical formulations adapted for parenteral administrationinclude aqueous and non-aqueous sterile injection solutions comprisingantioxidants, buffers, bacteriostatics and solutes, by means of whichthe formulation is rendered isotonic with the blood of the recipient tobe treated; and aqueous and non-aqueous sterile suspensions, which maycomprise suspension media and thickeners. The formulations can beadministered in single-dose or multidose containers, for example sealedampoules and vials, and stored in freeze-dried (lyophilised) state, sothat only the addition of the sterile carrier liquid, for example waterfor injection purposes, immediately before use is necessary.

Injection solutions and suspensions prepared in accordance with therecipe can be prepared from sterile powders, granules and tablets.

It goes without saying that, in addition to the above particularlymentioned constituents, the formulations may also comprise other agentsusual in the art with respect to the particular type of formulation;thus, for example, formulations which are suitable for oraladministration may comprise flavours.

A therapeutically effective amount of a compound of the presentinvention depends on a number of factors, including, for example, theage and weight of the human or animal, the precise condition requiringtreatment, and its severity, the nature of the formulation and themethod of administration, and is ultimately determined by the treatingdoctor or vet. However, an effective amount of a compound according tothe invention for the treatment is generally in the range from 0.1 to100 mg/kg of body weight of the recipient (mammal) per day andparticularly typically in the range from 1 to 10 mg/kg of body weightper day. Thus, the actual amount per day for an adult mammal weighing 70kg is usually between 70 and 700 mg, where this amount can beadministered as an individual dose per day or usually in a series ofpart-doses (such as, for example, two, three, four, five or six) perday, so that the total daily dose is the same. An effective amount of asalt or solvate or of a physiologically functional derivative thereofcan be determined as the fraction of the effective amount of thecompound according to the invention per se. It can be assumed thatsimilar doses are suitable for the treatment of other conditionsmentioned above.

The invention furthermore relates to medicaments comprising at least onecompound according to the invention and/or pharmaceutically usablederivatives, solvates and stereoisomers thereof, including mixturesthereof in all ratios, and at least one further medicament activeingredient.

Further medicament active ingredients are preferably chemotherapeuticagents, in particular those which inhibit angiogenesis and thus inhibitthe growth and spread of tumour cells; preference is given here to VEGFreceptor inhibitors, including robozymes and antisense which aredirected to VEGF receptors, and angiostatin and endostatin.

Examples of antineoplastic agents which can be used in combination withthe compounds according to the invention generally include alkylatingagents, antimetabolites; epidophyllotoxin; an antineoplastic enzyme; atopoisomerase inhibitor; procarbazin; mitoxantron or platinumcoordination complexes.

Antineoplastic agents are preferably selected from the followingclasses: anthracyclins, vinca medicaments, mitomycins, bleomycins,cytotoxic nucleosides, epothilones, discodermolides, pteridines,diynenes and podophyllotoxins.

Particular preference is given in the said classes to, for example,caminomycin, daunorubicin, aminopterin, methotrexate, methopterin,dichloromethotrexate, mitomycin C, porfiromycin, 5-fluorouracil,6-mercaptopurine, gemcitabine, cytosinarabinoside, podophyllotoxin orpodophyllotoxin derivatives, such as, for example, etoposide, etoposidephosphate or teniposide, melphalan, vinblastine, vincristine,leurosidine, vindesine, leurosine and paclitaxel. Other preferredantineoplastic agents are selected from the group estramustine,carboplatin, cyclophosphamide, bleomycin, gemcitabine, ifosamide,melphalan, hexamethylmelamine, thiotepa, cytarabin, idatrexate,trimetrexate, dacarbazine, L-asparaginase, camptothecin, CPT-11,topotecan, arabinosylcytosine, bicalutamide, flutamide, leuprolide,pyridobenzoindole derivatives, interferons and interleukins.

The invention also relates to a set (kit) consisting of separate packsof

-   (a) an effective amount of a compound according to the invention    and/or pharmaceutically usable derivatives, solvates and    stereoisomers thereof, including mixtures thereof in all ratios, and-   (b) an effective amount of a further medicament active ingredient.

The set comprises suitable containers, such as boxes, individualbottles, bags or ampoules. The set may, for example, comprise separateampoules, each containing an effective amount of a compound according tothe invention and/or pharmaceutically usable derivatives, solvates andstereoisomers thereof, including mixtures thereof in all ratios, and aneffective amount of a further medicament active ingredient in dissolvedor lyophilised form.

Use

The present compounds are suitable as pharmaceutical active ingredientsfor mammals, in particular for humans, in the treatment of diseases inwhich HSP90 plays a role.

The invention thus relates to the use of the compounds according to theinvention, and pharmaceutically usable derivatives, solvates andstereoisomers thereof, including mixtures thereof in all ratios, for thepreparation of a medicament for the treatment of diseases in which theinhibition, regulation and/or modulation of HSP90 plays a role.

The present invention encompasses the use of the compounds according tothe invention and/or physiologically acceptable salts and solvatesthereof for the preparation of a medicament for the treatment of tumourdiseases, such as, for example, fibrosarcoma, myxosarcoma, liposarcoma,chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma,endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma,synovioma, mesothelioma, Ewing's tumour, leiosarcoma, rhabdomyosarcoma,colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer,prostate cancer, squamous cell carcinoma, basal cell carcinoma,adenocarcinoma, syringocarcinoma, sebaceous gland carcinoma, papillarycarcinoma, papillary adenocarcinomas, cystadenocarcinomas, bone marrowcarcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bileduct carcinoma, choriocarcinoma, seminoma, embryonic carcinoma, Wilm'stumour, cervical cancer, testicular tumour, lung carcinoma, small-celllung carcinoma, bladder carcinoma, epithelial carcinoma, glioma,astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma,haemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma,melanoma, neuroblastoma, retinoblastoma, leukaemia, lymphoma, multiplemyeloma, Waldenström's macroglobulinaemia and heavy chain disease;

viral diseases, where the viral pathogen is selected from the groupconsisting of hepatitis type A, hepatitis type B, hepatitis type C,influenza, varicella, adenovirus, herpes simplex type I (HSV-I), herpessimplex type II (HSV-II), cattle plague, rhinovirus, echovirus,rotavirus, respiratory syncytial virus (RSV), papillomavirus,papovavirus, cytomegalovirus, echinovirus, arbovirus, huntavirus,Coxsackie virus, mumps virus, measles virus, rubella virus, polio virus,human immunodeficiency virus type I (HIV-I) and human immunodeficiencyvirus type II (HIV-II);for immune suppression in transplants; inflammation-induced diseases,such as rheumatoid arthritis, asthma, multiple sclerosis, type 1diabetes, lupus erythematosus, psoriasis and inflammatory bowel disease;cystic fibrosis; diseases associated with angiogenesis, such as, forexample, diabetic retinopathy, haemangiomas, endometriosis, tumourangiogenesis; infectious diseases; autoimmune diseases; ischaemia;promotion of nerve regeneration; fibrogenetic diseases, such as, forexample, scierodermatitis, polymyositis, systemic lupus, cirrhosis ofthe liver, keloid formation, interstitial nephritis and pulmonaryfibrosis;

The compounds according to the invention can inhibit, in particular, thegrowth of cancer, tumour cells and tumour metastases and are thereforesuitable for tumour therapy.

The present invention furthermore encompasses the use of the compoundsaccording to the invention and/or physiologically acceptable salts andsolvates thereof for the preparation of a medicament for the protectionof normal cells against toxicity caused by chemotherapy, and for thetreatment of diseases in which incorrect protein folding or aggregationis a principal causal factor, such as, for example, scrapie,Creutzfeldt-Jakob disease, Huntington's or Alzheimer's

The invention also relates to the use of the compounds according to theinvention and/or physiologically acceptable salts and solvates thereoffor the preparation of a medicament for the treatment of diseases of thecentral nervous system, of cardiovascular diseases and cachexia.

In a further embodiment, the invention also relates to the use of thecompounds according to the invention and/or physiologically acceptablesalts and solvates thereof for the preparation of a medicament for HSP90modulation, where the modulated biological HSP90 activity causes animmune reaction in an individual, protein transport from theendoplasmatic reticulum, recovery from hypoxiclanoxic stress, recoveryfrom malnutrition, recovery from heat stress, or combinations thereofand/or where the disorder is a type of cancer, an infectious disease, adisorder associated with disrupted protein transport from theendoplasmatic reticulum, a disorder associated withischaemia/reperfusion, or combinations thereof, where the disorderassociated with ischaemia/reperfusion is a consequence of cardiacarrest, asystolia and delayed ventricular arrhythmia, heart operation,cardiopulmonary bypass operation, organ transplant, spinal cord trauma,head trauma, stroke, thromboembolic stroke, haemorrhagic stroke,cerebral vasospasm, hypotonia, hypoglycaemia, status epilepticus, anepileptic fit, anxiety, schizophrenia, a neurodegenerative disorder,Alzheimer's disease, Huntington's disease, amyotrophic lateral sclerosis(ALS) or neonatal stress.

In a further embodiment, the invention also relates to the use of thecompounds according to the invention and/or physiologically acceptablesalts and solvates thereof for the preparation of a medicament for thetreatment of ischaemia as a consequence of cardiac arrest, asystolia anddelayed ventricular arrhythmia, heart operation, cardiopulmonary bypassoperation, organ transplant, spinal cord trauma, head trauma, stroke,thromboembolic stroke, haemorrhagic stroke, cerebral vasospasm,hypotonia, hypoglycaemia, status epilepticus, an epileptic fit, anxiety,schizophrenia, a neurodegenerative disorder, Alzheimer's disease,Huntington's disease, amyotrophic lateral sclerosis (ALS) or neonatalstress.

Test Method for the Measurement of HSP90 Inhibitors

The binding of geldanamycin or 17-allylamino-17-demethoxygeldanamycin(17AAG) to HSP90 and competitive inhibition thereof can be utilised inorder to determine the inhibitory activity of the compounds according tothe invention (Carreras et al. 2003, Chiosis et al. 2002).

In the specific case, a radioligand filter binding test is used. Theradioligand used here is tritium-labelled 17-allylaminogeldanamycin,[3H]17AAG, This filter binding test allows a targeted search forinhibitors which interfere with the ATP binding site.

Material

Recombinant human HSP90α (E. coli expressed, 95% purity);

[3H]17AAG (17-allylaminogeldanamycin, [allylamino-2,3-³H. Specificactivity: 1.11×10¹² Bqμmol (Moravek, MT-1717);

HEPES filter buffer (50 mM HEPES, pH 7.0, 5 mM MgCl2, BSA 0.01%)Multiscreen FB (1 μm) filter plate (Millipore, MAFBNOB 50).

Method

The 96-well microtitre filter plates are firstly irrigated and coatedwith 0.1% of polyethylenimine.

The test is carried out under the following conditions:

Reaction temperature 22° C.

Reaction time: 30 min., shaking at 800 rpm

Test volume: 50 μl

Final concentrations:

50 mM HEPES HCl, pH 7.0, 5 mM MgCl2, 0.01% (w/v) of BSA

HSP90: 1.5 μg/assay

[3H]17AAG: 0.08 μM.

At the end of the reaction, the supernatant in the filter plate isremoved by suction with the aid of a vacuum manifold (MultiscreenSeparation System, Millipore), and the filter is washed twice.

The filter plates are then measured in a beta counter (Microbeta,Wallac) with scintillator (Microscint 20, Packard).

“% of control” is determined from the “counts per minutes” values, andthe IC-50 value of a compound is calculated therefrom.

TABLE I HSP90 inhibition by some representative compounds of the formulaI according to the invention Compound of the formula I IC₅₀ “A4” B “A6”A “A7” B “A10” B “A20” B “A23” A “A25” A “A26” B “A27” A “A28” A “A29” B“A30” B “A31” B “A32” B “A33” B “A34” C “A35” B “A36” A “A37” B “A38” B“A39” A “A40” A “A41” B “A42” A “A43” B “A44” B “A45” C “A52” B “A64” B“A71” B “A73” B “A101” A “A122” A “A130” A “A134” A “A137” A “A143” A“A144” A “A145” A “A147” A “A148” A “A152” A “A154” A “A157” A “A160” A“A162” A “A173” A “A174” A “A175” A “A176” A “A177” A “A178” A “A181” A“A182” B “A189” A “A190” A “A191” A “A192” A “A193” A “A194” A “A195” B“A256” A “A257” A “A260” A “A262” A IC₅₀: 10 nM-1 μM = A 1 μM-10 μM =B >10 mM = C

Above and below, all temperatures are indicated in ° C., In thefollowing examples, “conventional work-up” means: water is added ifnecessary, the pH is adjusted, if necessary, to values between 2 and 10,depending on the constitution of the end product, the mixture isextracted with ethyl acetate or dichloromethane, the phases areseparated, the organic phase is dried over sodium sulfate andevaporated, and the product is purified by chromatography on silica geland/or by crystallisation. Rf values on silica gel; eluent: ethylacetate/methanol 9:1.

LC-MS and HPLC Conditions

The M+H⁺ data given in the following examples are the measurementresults of the LC-MS measurements:

Hewlett Packard system from the HP 1100 series with the followingfeatures: ion source: electrospray (positive mode); scan: 100-1000 m/e;fragmentation voltage: 60 V; gas temperature: 300° C., DAD: 220 nm.

Flow rate: 2.4 ml/min. The splitter used reduced the flow rate for MSafter the DAD to 0.75 ml/min.

Column: Chromolith SpeedROD RP-18e 50-4.6

Solvents: LiChrosolv grade from Merck KGaA

Solvent A: H2O (0.01% of TFA)

Solvent B: ACN (0.008% of TFA)

The retention times Rt [min] given in the following examples are themeasurement results of the HPLC measurements:

P Gradient:

5.5 min; flow rate: 2.75 ml/min from 99:1 to 0:100 water/acetonitrile

Water+TFA (0.01% by vol.); acetonitrile+TFA (0.01% by vol.)

Column: Chromolith SpeedROD RP 18e 50-4.6

Wavelength: 220 nm

N Gradient:

5.5 min; flow rate: 2.75 ml/min from 90:10 to 0:100 water/acetonitrile

Water+TFA (0.01% by vol.); acetonitrile+TFA (0.01% by vol.)

Column: Chromolith SpeedROD RP 18e 50-4.6

Wavelength: 220 nm

EXAMPLE 1

1.1 50 ml of DMF are added under argon to 6.0 g of4-fluoro-2-hydroxybenzoic acid and 4.52 g of potassiumhydrogencarbonate, and the mixture is stirred for 10 minutes. 3.05 ml ofiodomethane are added dropwise, and the mixture is stirred at 40° for 3hours. The mixture is poured into 150 ml of water and subjected toconventional work-up, giving 6.48 g of methyl 4-fluoro-2-hydroxybenzoate(“1a”).

1.2 5 ml of dichloromethane are added under argon to 1.06 g of aluminiumchloride, and the mixture is cooled to 0° with stirring. 940 μl ofphenylacetyl chloride are added dropwise, followed by a solution of 695mg of “11a” in 5 ml of dichloromethane. The mixture is stirred at 0° for10 minutes, then at RT for 16 hours.

The mixture is cooled to 0°, hydrolysed using 1 N HCl and subjected toconventional work-up. For purification, the residue is chromatographedover a 40 g silica-gel column, giving 323 mg of methyl4-fluoro-2-hydroxy-5-phenylacetylbenzoate (“11b”)

1.3 270 μl of hydrazinium hydroxide are added to a solution of 323 mg of“1b” in 5 ml of 1,4-dioxane, and the mixture is heated under reflux for30 minutes. The solvent is removed, and the mixture is subjected toconventional work-up, giving 280 mg of methyl3-benzyl-6-hydroxy-1H-indazole-5-carboxylate (“A1”)

1.4 595 μl of 2 N NaOH are added to a suspension of 112 mg of “A1” in1.5 ml of methanol, and the mixture is stirred at 60° for 3 hours. Themixture is cooled, 0.7 ml of 2 N HCl is added, the mixture is dilutedwith water, the precipitate is removed, and the mixture is subjected toconventional work-up, giving 75 mg of3-benzyl-6-hydroxy-1H-indazole-5-carboxylic acid (“A2”).

EXAMPLE 2

2.1 1.5 ml of ammonia (7 M in methanol) are added under argon to 30 mgof “A1”, and the mixture is stirred in the microwave at 100°/10 bar for40 minutes. 0.5 ml of ammonia solution (32%) and 5.06 mg of magnesiumchloride are added, and the mixture is stirred at 120°/17 bar for afurther 40 minutes. The mixture is subjected to conventional work-up,and the residue is chromatographed over an RP18 silica-gel column,giving 2.7 mg of 5-aminocarbonyl-3-benzyl-6-hydroxy-1H-indazole (“A3”).

RT [min] (HPLC) Compound Name (gradient) M + H⁺ “A3”5-Aminocarbonyl-3-benzyl-6- 2.65 268 hydroxy-1H-indazole (P)

EXAMPLE 3

3.1 0.5 ml of DMF is added under argon to 20 mg of “A2”, 19 μl ofN-methyl-N-propylamine, 57 mg of EDCl[N-ethyl-N,N′-(dimethylaminopropyl)carbodiimide]×HCl and 25 mg of HOBt(1-hydroxybenzotriazole) x H₂O, and 101.4 μl of N-ethyldiisopropylamineare added dropwise. The mixture is stirred at RT for 45 hours.

The mixture is subjected to conventional work-up, and the residue ischromatographed over an RP18 silica-gel column, giving 9.6 mg of5-(N-propyl-N-methylaminocarbonyl)-3-benzyl-6-hydroxy-1H-indazole(“A4”).

RT [min] (HPLC) Compound Name (gradient) M + H⁺ “A4”5-(N-Propyl-N-methylamino- 2.83 324 carbonyl)-3-benzyl-6- (P)hydroxy-1H-indazole

The following compounds are obtained analogously

RT [min] (HPLC) Compound Name/structure (gradient) M + H⁺ “A5”5-(N-Butyl-N-methylaminocarbonyl)-3-benzyl-6- 2.97 338hydroxy-1H-indazole (P) “A6”5-(N-Benzyl-N-methylaminocarbonyl)-3-benzyl-6- 3.02 372hydroxy-1H-indazole (P) “A7”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3- 2.65 340benzyl-6-hydroxy-1H-indazole (P)

“A8” 5-[N-(3-Methylbenzyl)-N-methylaminocarbonyl]-3- 3.09 386benzyl-6-hydroxy-1H-indazole (P)

“A9” 5-[N-(2-Chlorobenzyl)-N-methylaminocarbonyl]-3- 3.11 406benzyl-6-hydroxy-1H-indazole (P) “A10”5-[N-(3-Chlorobenzyl)-N-methylaminocarbonyl]-3- 3.11 406benzyl-6-hydroxy-1H-indazole (P) “A11”5-[N-(2-Fluorobenzyl)-N-methylaminocarbonyl]-3- 3.03 390benzyl-6-hydroxy-1H-indazole (P) “A12”5-[N-(3-Fluorobenzyl)-N-methylaminocarbonyl]-3- 3.02 390benzyl-6-hydroxy-1H-indazole (P) “A13”5-[N-(2-Bromobenzyl)-N-methylaminocarbonyl]-3- 3.15 451benzyl-6-hydroxy-1H-indazole (P) “A14”5-[N-(2-Methylbenzyl)-N-methylaminocarbonyl]-3- 2.16 386benzyl-6-hydroxy-1H-indazole (N) “A15”5-[N-(4-Fluorobenzyl)-N-methylaminocarbonyl]-3- 3.02 390benzyl-6-hydroxy-1H-indazole (P) “A16”5-[N-(2-Methoxybenzyl)-N-methylaminocarbonyl]-3- 3.03 402benzyl-6-hydroxy-1H-indazole (P) “A17”5-[N-(4-Methylbenzyl)-N-methylaminocarbonyl]-3- 2.19 386benzyl-6-hydroxy-1H-indazole (N) “A18”5-[N-(4-Chlorobenzyl)-N-methylaminocarbonyl]-3- 3.13 406benzyl-6-hydroxy-1H-indazole (P) “A19”5-[N-(3,4-Dichlorobenzyl)-N-methylaminocarbonyl]-3- 2.39 441benzyl-6-hydroxy-1H-indazole (N) “A20”5-[N-(2-Methoxy-5-methylbenzyl)-N- 2.25 416methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole (N) “A21”5-[N-(2,4-Dimethylbenzyl)-N-methylaminocarbonyl[-3- 2.35 400benzyl-6-hydroxy-1H-indazole (N) “A22”5-[N-(4-Ethoxybenzyl)-N-methylaminocarbonyl]-3- 2.23 416benzyl-6-hydroxy-1H-indazole (N) “A23”5-[N-(2,3-Dimethoxybenzyl)-N-methylaminocarbonyl]-3- 2.05 432benzyl-6-hydroxy-1H-indazole (N) “A24”5-[N-(4-Bromobenzyl)-N-methylaminocarbonyl]-3- 2.29 451benzyl-6-hydroxy-1H-indazole (N) “A26”5-[N-(3-Bromobenzyl)-N-methylaminocarbonyl]-3- 3.17 451benzyl-6-hydroxy-1H-indazole (P) “A27”5-[N-(3-Methoxybenzyl)-N-methylaminocarbonyl]-3- 3.01 452benzyl-6-hydroxy-1H-indazole (P) “A28”5-[N-(4-Ethylbenzyl)-N-methylaminocarbonyl]-3-benzyl- 2.37 4006-hydroxy-1H-indazole (N) “A29” 5-[N-(3-Trifluoromethylbenzyl)-N- 2.29440 methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole (N) “A30”5-[N-(Benzo-1,3-dioxol-4-ylmethyl)-N- 2   416methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole (N) “A31”5-[N-(3-Chloro-6-methoxybenzyl)-N- 2.26 436methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole (N)

EXAMPLE 4

4.1 12 ml of dichloromethane are added under argon to 3.25 g ofaluminium chloride, and the mixture is cooled to −55° C. with stirring.A solution of 2.5 g of 2-bromo-5-fluoroanisole and 2.47 g ofmtolylacetyl chloride in 8 ml of dichloromethane is added dropwise atthis temperature. The mixture is stirred for a further 10 minutes,allowed to warm slowly to 0° C. and subsequently hydrolysed using 1 NHCl. The mixture is stirred for a further 15 minutes, diluted withdichloromethane and subjected to conventional work-up. The residueobtained is digested with petroleum ether/diethyl ether (8:2), filteredoff with suction and rinsed with petroleum ether. Drying gives 1.85 g of“4a”

4.2 0.74 ml of hydrazinium hydroxide is added to a suspension of 1.85 gof “4a” in 10 ml of dioxane, and the mixture is heated under reflux for2.5 hours. The mixture is cooled, ethyl acetate and 1 N Hcl are added,and the mixture is subjected to conventional work-up. The residue ischromatographed over silica gel, giving 1.24 g of5-bromo-6-methoxy-3-(3-methylbenzyl)-1H-indazole (“4b”)

4.3 1.24 g of “4b” are dissolved in 12 ml of dichloromethane under argonand cooled to 0° C. 3.45 ml of boron tribromide are added dropwise, andthe mixture is stirred at room temperature for a further 16 hours. Themixture is subjected to conventional work-up, and the residue is, forfurther purification, chromatographed over a 120 g RP18 silica-gelcolumn, giving 578 mg of5-bromo-6-hydroxy-3-(3-methylbenzyl)-1H-indazole (“4c”).

4.4 Reaction in an autoclave at 100°/4-6 bar/22 hours:

578 mg of “4c”, 25 ml of methanol, 300 mg of triethylamine, 25 ml oftoluene are initially introduced and degassed. 15 mg of(1,1′-bis(diphenylphosphino)ferrocene)dichloropalladium(II) are thenadded. The autoclave is decompressed, CO is injected at 4 bar, and theautoclave is heated to 100°.

Removal of the solvents gives5-methoxycarbonyl-6-hydroxy-3-(3-methylbenzyl)-1H-indazole (“4d”).

4.5 4.23 ml of 2 N NaOH are added to a solution of 523 mg of “4d” in 10ml of dioxane, and the mixture is heated under reflux for 1.5 hours. Themixture is subjected to conventional work-up, giving 386 mg of5-carboxy-6-hydroxy-3-(3-methylbenzyl)-1H-indazole (“4e”).

4.6 0.1 ml of thionyl chloride is added to a suspension of 200 mg of“4e” in 4 ml of THF, and the mixture is stirred for a further hour. 3 mlof toluene are added, and the solvents are removed at 300, giving5-chlorocarbonyl-6-hydroxy-3-(3-methylbenzyl)-1H-indazole (“4f”)

4.7 A solution of 52 mg of “4f” in 1 ml of THF is added dropwise to asolution of 18.65 mg of N-methylbutylamine and 88.2 μl ofN-ethyldiisopropylamine in 2 ml of THF. The mixture is stirred for afurther 1 hour and subjected to conventional work-up. For furtherpurification, the residue is chromatographed over an RP18 silica-gelcolumn, giving 18.8 mg of5-(N-butyl-N-methylaminocarbonyl)-3-(3-methylphenyl)-6-hydroxy-1H-indazole(“A25”)

“A25”

RT [min] (HPLC) Compound Name (gradient) M + H⁺ “A25”5-(N-Butyl-N-methylaminocarbonyl)- 2.13 3523-(3-methylbenzyl)-6-hydroxy-1H- (N) indazole

The following compounds are obtained analogously

RT [min] (HPLC) Compound Name/structure (gradient) M + H⁺ “A32”5-(N-Benzyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H- 2.19406 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.23 (s, 1H,broad), 9.73 (s, 1H), 7.43-7.17 (m, 10H), 6.84 (s, 1H), 4.53 (s, 2H,broad), 4.29 (s, 2H), 2.76 (s, 3H) “A33”5-(N-Butyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H- 2.14372 indazole (N) “A34”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(2-chlorobenzyl)-6- 1.72374 hydroxy-1H-indazole (N) “A35”5-(N-Propyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H- 1.95358 indazole (N) “A36”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H- 2.21386 indazole (N) “A37”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 1.71354 hydroxy-1H-indazole (N) “A38”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H- 1.96338 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.15 (s, 1H,broad), 9.54 (s, 1H), 7.24 (s, 1H), 7.16-7.03 (m, 3H), 6.92 (d, 1H),6.78 (s, 1H), 7.13 (s, 2H), 3.4 (t, 2H), 2.83 (s, 3H), 1.55-1.41 (m,2H), 0.74 (t, 3H) “A39”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H- 2.15372 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.21 (s, 1H,broad), 9.58 (s, 1H), 7.35-7.18 (m, 5H), 6.81 (s, 1H), 4.2 (s, 2H), 3.24(t, 2H), 2.84 (s, 3H), 1.52-1.4 (m, 2H), 1.25-1.1 (m, 2H), 0.77 (t, 3H)“A40”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H- 2.25406 indazole (N) “A41”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6- 1.79374 hydroxy-1H-indazole (N) “A42”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H- 2.02358 indazole (N) “A43”5-(N-Butyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H- 2.13352 indazole (N) “A44”5-(N-Benzyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H- 2.21386 indazole (N) “A45”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl-3-(2-methylbenzyl)-6- 1.69354 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.17(s, 1H, broad), 9.58 (s, 1H), 7.25 (s, 1H), 7.22-7.1 (m, 4H), 6.83 (s,1H), 4.19 (s, 2H), 3.44 (s, 4H), 3.22 (s, 3H), 2.92 (s, 3H), 2.34 (s,3H) “A46”5-(N-Propyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H- 1.95338 indazole (N) “A47”5-[N-(Furan-2-ylmethyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-1.98 362 indazole (N) “A48”5-[N-(4-Chloro-3-methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6- 2.26436 hydroxy-1H-indazole (N) “A49”5-[N-(3,4-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-1.91 432 indazole (N) “A50”5-[N-(4-Methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-2.13 402 indazole (N) “A51”5-[N-(4-Chloro-3-fluorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-2.38 425 1H-indazole (N) “A52”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-2.03 356 1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.2 (s,1H, broad), 9.57 (s, 1H), 7.32 (s, 1H), 6.97 (s, 1H), 6.9-6.78 (m, 3H),4.19 (s, 2H), 3.26 (t, 2H), 2.88 (s, 3H), 2.28 (s, 3H), 1.59-1.47 (m,2H), 0.79 (t, 3H) “A53”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-2.29 404 1H-indazole (N) “A54”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-2.19 370 1H-indazole (N) “A55”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H- 2.10356 indazole (N) “A56”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H- 2.19390 indazole (N) “A57”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H- 1.93342 indazole (N) “A58”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H-indazole2.37 366 (N) “A59”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H- 2.41400 indazole (N) “A60”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H- 2.19352 indazole (N) “A61”5-(N-Butyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H- 2.21372 indazole (N) “A62”5-(N-Benzyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H- 2.28406 indazole (N) “A63”5-(N-Propyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H- 2.05358 indazole (N) “A64”5-(N-Butyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H- 2.17352 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.07 (s, 1H,broad), 9.44 (s, 1H), 7.25 (s, 1H), 7.17 (d, 2H), 7.06 (d, 2H), 6.83 (s,1H), 4.15 (s, 2H), 3.28 (t, 2H), 2.86 (s, 3H), 2.26 (s, 3H), 1.56-1.43(m, 2H), 1.3-1.14 (m, 2H), 0.82 (t, 3H) “A65”5-(N-Benzyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H- 2.22386 indazole (N) “A66”5-(N-Propyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H- 1.99338 indazole (N) “A67”5-(N-Propyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-2.19 393 indazole (N) “A68”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-2.41 441 indazole (N) “A69”5-(N-Butyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-2.33 407 indazole (N) “A70”5-(N-Butyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H-indazole2.35 366 (N) “A71”5-(N-Benzyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H- 2.41400 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.11 (s, 1H,broad), 9.64 (s, 1H), 7.35-7.21 (m, 6H), 7.16 (d, 2H), 7.06 (d, 2H),6.82 (s, 1H), 4.53 (s, 2H), 4.12 (s, 2H), 2.76 (s, 3H), 2.54 (q, 2H),1.24 (t, 3H) “A72”5-(N-Propyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H- 2.19352 indazole (N) “A73”5-(N-Propyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-2.13 352 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.13 (s, 1H,broad), 9.57 (s, 1H), 7.22 (s, 1H), 7.03 (s, 1H), 7.01-6.93 (m, 2H),6.78 (s, 1H), 4.08 (s, 2H), 3.27-3.15 (m, 2H), 2.83 (s, 3H), 2.15 (s,6H), 1.54-1.42 (m, 2H), 0.75 (t, 3H) “A74”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-2.35 400 indazole (N) “A75”5-(N-Butyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-2.31 366 indazole (N) “A76”5-[N-(4-Chloro-3-methoxybenzyl)-N-methylaminocarbonyl]-3-(3- 2.40 471chlorobenzyl)-6-hydroxy-1H-indazole (N) “A77”5-[N-(3,4-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-2.08 466 hydroxy-1H-indazole (N) “A78”5-[N-(4-Methoxybenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6- 2.23436 hydroxy-1H-indazole (N) “A79”5-[N-(Benzo-1,3-dioxol-5-ylmethyl)-N-methylaminocarbonyl]-3-(3- 2.27 451chlorobenzyl)-6-hydroxy-1H-indazole (N) “A80”5-[N-(3-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-2.35 424 1H-indazole (N) “A81”5-[N-(2-Bromobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-2.52 485 1H-indazole (N) “A82”5-[N-(2,3-Dihydrobenzo-1,4-dioxin-6-ylmethyl)-N-methylaminocarbonyl]-3-(3-2.25 465 chlorobenzyl)-6-hydroxy-1H-indazole (N)

“A83”5-[N-(4-Chloro-3-fluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-2.55 459 hydroxy-1H-indazole (N) “A84”5-[N-(3-Methylsulfonylaminobenzyl)-N-methylaminocarbonyl]-3-(3- 2.03 499chlorobenzyl)-6-hydroxy-1H-indazole (N) “A85”5-[N-(3-Methylsulfonylaminomethylbenzyl)-N-methylaminocarbonyl]-3-(3-1.96 514 chlorobenzyl)-6-hydroxy-1H-indazole (N) “A86”5-(N-Benzyl-N-ethylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H- 2.41421 indazole (N) “A87”5-[N-(2,4-Difluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-2.40 442 hydroxy-1H-indazole (N) “A88”5-[N-(4-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-2.35 424 1H-indazole (N) “A89”5-[N-(Furan-2-ylmethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.15 396 hydroxy-1H-indazole (N) “A90”5-[N-(2-Bromobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.44465 hydroxy-1H-indazole (N) “A91”5-[N-(3-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.27404 hydroxy-1H-indazole (N) “A92”5-[N-(4-Methylbenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.37400 hydroxy-1H-indazole (N) “A93”5-[N-(4-Chlorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.42420 hydroxy-1H-indazole (N) “A94”5-[N-(4-Ethylbenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-2.53 414 1H-indazole (N) “A95”5-[N-(2,3-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.22 445 hydroxy-1H-indazole (N) “A96”5-[N-(Benzo-1,3-dioxol-5-ylmethyl)-N-methylaminocarbonyl]-3-(3- 2.17 430methylbenzyl)-6-hydroxy-1H-indazole (N) “A97”5-[N-(4-Methylbenzyl)-N-ethylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-2.48 414 1H-indazole (N) “A98”5-[N-(4-Chloro-3-methoxybenzyl)-N-methylaminocarbonyl]-3-(3- 2.40 450methylbenzyl)-6-hydroxy-1H-indazole (N) “A99”5-[N-(3,4-Dimethoxybenzyl)-N-methylaminocarbonyl]-(3-methylbenzyl)-6-2.04 446 hydroxy-1H-indazole (N) “A100”5-[N-(4-Methoxybenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.19416 hydroxy-1H-indazole (N) “A101”5-[N-(2,3-Dihydrobenzo-1,4-dioxin-6-ylmethyl)-N-methylaminocarbonyl]-3-(3-2.19 444 methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80°C.): δ [ppm] = 12.18 (s, 1H, broad), 9.72 (s, 1H), 7.32 (s, 1H),7.15-7.02 (m, 3H), 6.91 (d, 1H), 6.82 (s, 1H), 6.77 (d, 2H), 6.73-6.66(m, 1H), 4.4 (s, 2H, broad), 4.21 (s, 4H), 4.13 (s, 2H), 2.73 (s, 3H),2.22 (s, 3H) “A102”5-[N-(4-Chloro-3-fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-2.48 438 6-hydroxy-1H-indazole (N) “A103”5-(N-Benzyl-N-ethylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H- 2.39400 indazole (N) “A104”5-[N-(3-Methylsulfonylaminobenzyl)-N-methylaminocarbonyl]-3-(3- 1.99 479methylbenzyl)-6-hydroxy-1H-indazole (N) “A105”5-[N-(4-Methylsulfonylaminomethylbenzyl)-N-methylaminocarbonyl]-3-(3-1.91 493 methylbenzyl)-6-hydroxy-1H-indazole (N) “A106”5-[N-(4-Methylsulfonylaminobenzyl)-N-methylaminocarbonyl]-3-(3- 1.91 479methylbenzyl)-6-hydroxy-1H-indazole (N) “A107”5-[N-(2,4-Difluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.38 422 hydroxy-1H-indazole (N) “A108”5-[N-(4-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.29404 hydroxy-1H-indazole (N) “A109”5-[N-(4-Chloro-2-fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-2.51 438 6-hydroxy-1H-indazole (N) “A110”5-[N-(3,4-Difluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.36 422 hydroxy-1H-indazole (N) “A111”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-methoxybenzyl)-6-hydroxy-1H-2.10 402 indazole (N) “A112”5-[N-(4-Chlorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.71406 hydroxy-1H-indazole (N) “A113”5-[N-(4-Methylbenzyl)aminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-2.67 386 indazole (N) “A114”5-[N-(Furan-2-ylmethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.09 376 hydroxy-1H-indazole (N) “A115”5-(N-Benzylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-indazole 2.51372 (N) “A116”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H- 2.23372 indazole (N) “A117”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H- 2.26392 indazole (N) “A118”5-(N-Phenyl-N-methylaminocarbonyl)-3-benzyl-6-hydroxy-1H-indazole 2.07358 (N) “A119”5-(N-Phenyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H- 2.20372 indazole (N) “A120”5-(N-Phenyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H- 2.24392 indazole (N) “A121”5-(N-Phenyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H- 2.27392 indazole (N) “A122”5-(N-Phenyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H- 2.22372 indazole (N) “A123”5-(N-Phenyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H- 2.36386 indazole (N) “A124”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-2.45 427 indazole (N) “A125”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-2.33 386 indazole (N) “A126”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-2.25 390 1H-indazole (N) “A127”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H- 2.13376 indazole (N) “A128”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H- 2.37386 indazole (N) “A129”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-methoxybenzyl)-6-hydroxy-1H-2.06 388 indazole (N) “A130”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.19402 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.22(s, 1H, broad), 9.85 (s, 1H), 7.24 (s, 1H), 7.14 (t, 1H), 7.12-6.95 (m,5H), 6.69 (d, 2H), 6.59 (s, 1H), 4.01 (s, 2H), 3.62 (s, 3H), 3.23 (s,3H), 2.24 (s, 3H) “A131”5-[N-(2-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.38386 hydroxy-1H-indazole (N) “A132”5-[N-(2-Chlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.39406 hydroxy-1H-indazole (N) “A133”5-[N-(2-Fluorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.23390 hydroxy-1H-indazole (N) “A134”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-1.89 479 methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80°C.): δ [ppm] = 12.04 (s, 1H, broad), 9.62 (s, 1H), 7.26-7.18 (m, 2H),7.17-7.07 (m, 5H), 7.03 (s, 1H), 6.98 (t, 2H), 6.61 (s, 1H), 4.05-3.98(m, 4H), 3.28 (s, 3H), 2.57 (s, 3H), 2.26 (s, 3H) “A135”5-[N-(3-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.39386 hydroxy-1H-indazole (N) “A136”5-[N-(4-Chlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.37406 hydroxy-1H-indazole (N) “A137”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.36386 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.06(s, 1H, broad), 9.67 (s, 1H), 7.18 (s, 1H), 7.12 (t, 1H), 7.05-6.92 (m,7H), 6.63 (s, 1H), 3.99 (s, 2H), 3.26 (s, 3H), 2.25 (s, 3H), 2.17 (s,3H) “A138”5-[N-(3-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.27402 hydroxy-1H-indazole (N) “A139”5-[N-(4-Fluorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.25390 hydroxy-1H-indazole (N) “A140”5-[N-(4-Trifluoromethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-2.49 440 6-hydroxy-1H-indazole (N) “A141”5-[N-(3-Chlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.44406 hydroxy-1H-indazole (N) “A142”5-[N-(3,4-Dichlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.56 441 hydroxy-1H-indazole (N) “A143”5-[N-(2,3-Dihydrobenzo-1,4-dioxin-6-yl)-N-methylaminocarbonyl]-3-(3-2.27 430 methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80°C.): δ [ppm] = 12.08 (s, 1H, broad), 9.74 (s, 1H), 7.21 (s, 1H), 7.12(t, 1H), 7.03 (s, 1H), 6.96 (t, 2H), 6.71 (s, 1H), 6.66 (s, 1H), 6.51(s, 2H), 4.12 (s, 4H), 4.02 (s, 2H), 3.23 (s, 3H), 2.25 (s, 3H) “A144”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.25 416 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =12.08 (s, 1H, broad), 9.69 (s, 1H), 7.22 (s, 1H), 7.12 (t, 1H), 7.03 (s,1H), 6.97 (t, 2H), 6.76 (d, 1H), 6.68-6.57 (m, 3H), 5.9 (s, 2H), 4.02(s, 2H), 3.24 (s, 3H), 2.24 (s, 3H) “A145”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.07 432 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =12.21 (s, 1H, broad), 9.7 (s, 1H), 7.23 (s, 1H), 7.11 (t, 1H), 7.01 (s,1H), 6.95 (t, 2H), 6.78 (s, 1H), 6.74-6.65 (m, 2H), 6.63 (s, 1H), 4.0(s, 2H), 3.63 (s, 3H), 3.53 (s, 3H), 3.27 (s, 3H), 2.23 (s, 3H) “A146”5-[N-(4-Chloro-3-methoxyphenyl)-N-methylaminocarbonyl]-3-(3- 2.37 436methylbenzyl)-6-hydroxy-1H-indazole (N) “A147”5-[N-(3-Chloro-4-methoxyphenyl)-N-methylaminocarbonyl]-3-(3- 2.37 436methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ[ppm] = 12.08 (s, 1H, broad), 9.65 (s, 1H), 7.32-7.23 (m, 2H), 7.13 (t,1H), 7.09-7.02 (m, 2H), 6.97 (d, 2H), 6.89 (d, 1H), 6.65 (s, 1H), 4.03(s, 2H), 3.75 (s, 3H), 3.25 (s, 3H), 2.24 (s, 3H) “A148”5-[N-(4-Acetylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.05414 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.26(s, 1H, broad), 9.84 (s, 1H), 7.75 (d, 2H), 7.35 (s, 1H), 7.27 (d, 2H),7.19-7.06 (m, 1H), 7.02 (s, 1H), 6.97 (d, 2H), 6.62 (s, 1H), 4.04 (s,2H), 3.34 (s, 3H), 2.46 (s, 3H), 2.23 (s, 3H) “A149”5-[N-(3-Acetylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.04414 hydroxy-1H-indazole (N) “A150”5-[N-(4-Methylsulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-1.86 450 hydroxy-1H-indazole (N) “A151”5-[N-(2,2-Difluorobenzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-2.45 452 methylbenzyl)-6-hydroxy-1H-indazole (N) “A152”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-2.10 457 6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =12.06 (s, 1H, broad), 9.75 (s, 1H), 7.19 (s, 1H), 7.13 (t, 1H),7.05-6.93 (m, 5H), 6.7 (d, 2H), 6.63 (s, 1H), 3.99 (s, 2H), 3.66 (t,4H), 3.24 (s, 3H), 3.0 (t, 4H), 2.25 (s, 3H) “A153”5-[N-(3-Fluorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.25390 hydroxy-1H-indazole (N) “A154”5-[N-(3-Trifluoromethoxyphenyl)-N-methylaminocarbonyl]-3-(3- 2.52 456methylbenzyl)-6-hydroxy-1H-indazole (N) “A155”5-[N-(3-Trifluoromethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-2.44 440 6-hydroxy-1H-indazole (N) “A156”5-[N-(3-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-1.88 479 methylbenzyl)-6-hydroxy-1H-indazole (N) “A157”5-[N-(1-Acetyl-2,3-dihydro-1H-indol-5-yl)-N-methylaminocarbonyl]-3-(3-1.86 455 methylbenzyl)-6-hydroxy-1H-indazole (N)

“A158”5-[N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-N-methylaminocarbonyl]-3-(3-1.97 455 methylbenzyl)-6-hydroxy-1H-indazole (N) “A159”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6- 2.15402 hydroxy-1H-indazole (N) “A160”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6-2.01 418 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =11.97 (s, 1H, broad), 9.6 (s, 1H), 7.21-7.11 (m, 2H), 7.06 (d, 2H),6.79-6.68 (m, 5H), 6.64 (s, 1H), 4.01 (s, 2H), 3.71 (s, 3H), 3.65 (s,3H), 3.25 (s, 3H) “A161”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-1.91 473 6-hydroxybenzyl)-6-hydroxy-1H-indazole (N) “A162”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-1.68 495 methoxybenzyl)-6-hydroxy-1H-indazole (N) “A163”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6-1.98 432 hydroxy-1H-indazole (N) “A164”5-(N-Benzyl-N-methylaminocarbonyl)-3-butyl-6-hydroxy-1H-indazole 2.05338 (N) “A165”5-(N-Phenyl-N-methylaminocarbonyl)-3-ethyl-6-hydroxy-1H-indazole 1.63296 (N) “A166”5-(N-Phenyl-N-methylaminocarbonyl)-3-butyl-6-hydroxy-1H-indazole 2.03324 (N) “A167”5-(N-Phenyl-N-methylaminocarbonyl)-3-propyl-6-hydroxy-1H-indazole 1.89310 (N) “A168”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H- 2.23338 indazole (N) “A169”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H- 2.01354 indazole (N) “A170”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-butyl-1.56 432 6-hydroxy-1H-indazole (N) “A171”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-1.97 368 indazole (N) “A172”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-1.76 384 indazole (N) “A173”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1.90 409 1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 11.95 (s,1H, broad), 9.94 (s, 1H), 7.24 (s, 1H), 7.06 (d, 2H), 6.76 (d, 2H), 6.64(s, 1H), 3.66 (t, 4H), 3.29 (s, 3H), 3.01 (t,4H), 2.65 (t, 2H),1.56-1.47 (m, 2H), 1.31-1.21 (m, 2H), 0.87 (t, 3H) “A174”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-1.57 370 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.11 (s, 1H,broad), 9.93 (s, 1H), 7.32 (s, 1H), 6.89 (s, 1H), 6.78-6.66 (m, 2H),6.61 (s, 1H), 3.63 (s, 3H), 3.59 (s, 3H), 3.31 (s, 3H), 2.65 (t, 2H),1.61-1.5 (m, 2H), 0.82 (t, 3H) “A175”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1.75 354 1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.13 (s,1H, broad), 9.91 (s, 1H), 7.33 (s, 1H), 6.88 (s, 1H), 6.75-6.58 (m, 3H),5.92 (s, 2H), 3.27 (s, 3H), 2.68 (t, 2H), 1.65-1.53 (m, 2H), 0.84 (t,3H) “A176”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1.71 395 1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 11.91 (s,1H, broad), 9.92 (s, 1H), 7.25 (s, 1H), 7.12 (d, 2H), 6.76 (d, 2H), 6.64(s, 1H), 3.67 (t, 4H), 3.3 (s, 3H), 3.02 (t, 4H), 2.62 (t, 2H), 1.6-1.5(m, 2H), 0.84 (t, 3H) “A177”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3- 1.39417 propyl-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =12.09 (s, 1H, broad), 9.83 (s, 1H), 7.44 (t, 1H), 7.34 (s, 1H), 7.2 (d,2H), 7.16 (d, 2H), 6.58 (s, 1H), 4.02 (d, 2H), 3.29 (s, 3H), 2.67 (t,2H), 2.54 (s, 3H), 1.64-1.54 (m, 2H), 0.86 (t, 3H) “A178”5-(N-Benzyl-N-methylaminocarbonyl)-3-propyl-6-hydroxy-1H-indazole 1.87324 (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.05 (s, 1H, broad), 9.7(s, 1H), 7.46 (s, 1H), 7.36-7.22 (m, 5H), 6.82 (s, 1H), 4.57 (s, 2H),2.82 (s, 3H), 2.77 (t, 2H), 1.75-1.65 (m, 2H), 0.92 (t, 3H) “A179”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-1.82 340 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 11.96 (s, 1H,broad), 9.88 (s, 1H), 7.36 (s, 1H), 7.14 (d, 2H), 6.77 (d, 2H), 6.64 (s,1H), 3.66 (s, 3H), 3.3 (s, 3H), 2.64 (t, 2H), 1.61-1.51 (m, 2H), 0.84(t, 3H) “A180”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H- 2.04324 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 11.96 (s, 1H,broad), 9.84 (s, 1H), 7.26 (s, 1H), 7.09 (d, 2H), 7.02 (d, 2H), 6.64 (s,1H), 3.32 (s, 3H), 2.64 (t, 2H), 2.19 (s, 3H), 1.6-1.5 (m, 2H), 0.84 (t,3H) “A181”5-(N-Benzyl-N-methylaminocarbonyl)-3-phenethyl-6-hydroxy-1H-indazole2.21 386 (N) “A182”5-(N-Propyl-N-methylaminocarbonyl)-3-phenethyl-6-hydroxy-1H-indazole1.98 338 (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.07 (s, 1H, broad),9.54 (s, 1H), 7.35 (s, 1H), 7.26-7.18 (m, 4H), 7.17-7.09 (m, 1H), 6.78(s, 1H), 3.26 (t, 2H), 3.13 (t, 2H), 3.06-2.98 (m, 2H), 2.86 (s, 3H),1.6-1.49 (m, 2H), 0.81 (t, 3H) “A183”5-(N-Butyl-N-methylaminocarbonyl)-3-phenethyl-6-hydroxy-1H-indazole 2.15352 (N) “A184”5-[N-(Tetrahydropyran-4-yl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-1.72 400 hydroxy-1H-indazole (N) “A185”5-[N-(Piperidin-4-yl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-2.41 399 1H-indazole (P) “A186”5-[N-(Tetrahydropyran-4-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-1.71 380 hydroxy-1H-indazole (N) “A187”5-[N-(Piperidin-4-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-2.35 379 1H-indazole (P) “A188”5-[N-(Cyclopropylmethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.07 350 hydroxy-1H-indazole (N) “A189”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-2.47 470 methylbenzyl)-6-hydroxy-1H-indazole (P) ¹H-NMR (DMSO-d₆, 80°C.): δ [ppm] = 12.06 (s, 1H, broad), 9.77 (s, 1H), 7.18 (s, 1H), 7.13(t, 1H), 7.04-6.93 (m, 5H), 6.69 (d, 2H), 6.63 (s, 1H), 3.98 (s, 2H),3.24 (s, 3H), 3.01 (t, 4H), 2.38 (t, 4H), 2.25 (s, 3H), 2.19 (s, 3H)“A190”5-{N-[3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-1.35 500 3-(3-methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆,80° C.): δ [ppm] = 12.05 (s, 1H, broad), 9.72 (s, 1H), 7.18 (s, 1H),7.12 (t, 1H), 7.02 (s, 1H), 6.98-6.92 (m, 2H), 6.75-6.6 (m, 4H), 3.97(s, 2H), 3.66 (s, 3H), 3.27 (s, 3H), 2.76 (t, 4H), 2.32 (t, 4H), 2.24(s, 3H), 2.17 (s, 3H) “A191”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-(3- 2.43471 methylbenzyl)-6-hydroxy-1H-indazole (P)

¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.05 (s, 1H, broad), 9.68 (s, 1H),7.17 (s, 1H), 7.15-7.06 (m, 5H), 7.04-6.93 (m, 3H), 6.62 (s, 1H), 3.98(s, 2H), 3.49 (t, 4H), 3.32 (s, 2H), 3.28 (s, 3H), 2.26 (s, 3H), 2.22(t, 4H) “A192”5-[N-(4-Bromophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- 2.30451 hydroxy-1H-indazole (N) “A193”5-{N-[4-(3-Cyanopropoxy)phenyl)phenyl]-N-methylaminocarbonyl}-3-(3- 2.10455 methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ[ppm] = 12.06 (s, 1H, broad), 9.68 (s, 1H), 7.2 (s, 1H), 7.15 (t, 1H),7.07 (d, 2H), 7.02 (s, 1H), 7.0-6.93 (m, 2H), 6.73 (d, 2H), 6.63 (s,1H), 4.01 (s, 2H), 3.93 (t, 2H), 3.25 (s, 3H), 2.56 (t, 2H), 2.25 (s,3H), 1.98-1.91 (m, 2H) “A194”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-(3- 1.72471 methylbenzyl)-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ[ppm] = 12.1 (s, 1H, broad), 9.75 (s, 1H), 7.28-7.16 (m, 5H), 7.13 (t,1H), 7.04 (s, 1H), 6.97 (d, 2H), 6.67 (s, 1H), 4.14 (s, 2H), 4.03 (s,2H), 3.91 (t, 2H), 3.6 (t, 2H), 3.29 (s, 3H), 2.25 (s, 3H) “A195”5-(N-Cyclohexyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-2.23 378 indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.14 (s, 1H,broad), 9.51 (s, 1H), 7.2 (s, 1H), 7.14-7.01 (m, 3H), 6.95 (d, 1H), 6.79(s, 1H), 4.12 (s, 2H), 3.78-3.56 (m, 1H), 2.73 (s, 3H), 2.22 (s, 3H),1.75-1.4 (m, 7H), 1.14-0.96 (m, 3H) “A196”5-[N-(1-Methylpiperidin-4-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-2.35 393 hydroxy-1H-indazole (P) “A197”5-[N-(4-Dimethylaminophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-1.94 415 6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =12.04 (s, 1H, broad), 9.81 (s, 1H), 7.17 (s, 1H), 7.12 (t, 1H), 7.04-6.9(m, 5H), 6.62 (s, 1H), 6.49 (d, 2H), 3.97 (s, 2H), 3.24 (s, 3H), 2.79(s, 6H), 2.25 (s, 3H) “A198”5-[N-(4-Aminocarbonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-1.44 415 6-hydroxy-1H-indazole (N) “A199”5-[N-(3-Methylsulfonylaminophenyl)-N-methylaminocarbonyl]-3-(3- 1.89 465methylbenzyl)-6-hydroxy-1H-indazole (N) “A200”5-[N-(4-Acetamidophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A201”5-[N-(3-Acetamidophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A202”5-[N-(3-Aminocarbonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A203”5-[N-(3-Aminosulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A204”5-[N-(4-Aminosulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A205”5-[N-(4-Cyanophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A206”5-[N-(3-Cyanophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A207”5-[N-(2-Oxo-2,3-dihydro-1H-benzimidazol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole

“A208”5-{N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A209”5-[N-(3-Methylsulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A210”5-{N-[4-(Morpholine-4-sulfonyl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A211”5-[N-(3H-Benzimidazol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole

“A212” 5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole

“A213” 5-{N-[4-(2-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A214”5-{N-[4-(2-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A215”5-{N-[4-(2-Oxo-1,3-oxazinan-3-yl)-phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole

“A216”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-(3- 1.35459 methylbenzyl)-6-hydroxy-1H-indazole (N)

¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 12.06 (s, 1H, broad), 9.7 (s, 1H),7.19 (s, 1H), 7.13 (t, 1H), 7.09-6.93 (m, 5H), 6.71 (d, 2H), 6.63 (s,1H), 4.0 (s, 2H), 3.93 (t, 2H), 3.25 (s, 3H), 2.55 (t, 2H), 2.25 (s,3H), 218 (s, 6H) “A217”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A218”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A219”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A220”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A221”5-(N-Phenyl-N-methylaminocarbonyl)-3-isobutyl-6-hydroxy-1H-indazole“A222”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A223”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A224”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A225”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A226”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A227”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A228”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl{-3-isobutyl-6-hydroxy-1H-indazole “A229”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A230”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A231”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A232”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A233”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A234”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A235”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A236”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A237”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A238”5-(N-Phenyl-N-methylaminocarbonyl)-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A239”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A240”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A241”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A242”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A243”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A244”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A245”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A246”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A247”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A248”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A249”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A250”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A251”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A252”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A253”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A254”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A255”5-(N-Phenyl-N-methylaminocarbonyl)-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A256”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6- 2.31364 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆): δ [ppm] = 12.11 (s, 1H,broad), 9.89 (s, 1H), 7.26 (s, 1H), 7.07 (d, 2H), 6.98 (d, 2H), 6.61 (s,1H), 3.3 (s, 3H), 2.65 (d, 2H), 2.16 (s, 3H), 2.1-1.99 (m, 1H),1.65-1.38 (m, 5H), 1.29-1.02 (m, 3H) “A257”5-[N-(3-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-2.17 380 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆): δ [ppm] = 12.11 (s,1H, broad), 9.92 (s, 1H), 7.29 (s, 1H), 7.08 (t, 1H), 6.82 (s, 1H), 6.76(d, 1H), 6.67-6.59 (m, 2H), 3.6 (s, 3H), 3.33 (s, 3H), 2.65 (d, 2H),2.1-1.99 (m, 1H), 1.61-1.39 (m, 5H), 1.3-1.02 (m, 3H) “A258”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-2.25 380 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =11.96 (s, 1H, broad), 9.86 (s, 1H), 7.24 (s, 1H), 7.13 (d, 2H), 6.76 (d,2H), 6.64 (s, 1H), 3.65 (s, 3H), 3.3 (s, 3H), 2.65 (d, 2H), 2.13-2.01(m, 1H), 1.62-1.41 (m, 5H), 1.19-1.06 (m, 3H) “A259”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A260”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-2.11 394 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆): δ [ppm] = 12.18 (s,1H, broad), 9.96 (s, 1H), 7.36 (s, 1H), 6.91 (s, 1H), 6.8-6.64 (m, 3H),5.97 (s, 2H), 3.35 (s, 3H), 2.74 (d, 2H), 2.21-2.09 (m, 1H), 1.7-1.45(m, 5H), 1.36-1.1 (m, 3H) “A261”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A262”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-2.08 435 6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆): δ [ppm] = 12.0 (s,1H, broad), 10.01 (s, 1H), 7.29 (s, 1H), 7.11 (d, 2H), 6.8 (d, 2H), 6.69(s, 1H), 3.71 (t, 4H), 3.34 (s, 3H), 3.06 (t, 4H), 2.68 (d, 2H),2.18-2.06 (m, 1H), 1.67-1.45 (m, 5H), 1.25-1.13 (m, 3H) “A263”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A264”5-[N-(4-Morpholin-4-ylmethylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A265”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3- 2.19 433cyclopentylmethyl-6-hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ[ppm] = 11.96 (s, 1H, broad), 9.81 (s, 1H), 7.26 (s, 1H), 7.13 (d, 2H),6.78 (d, 2H), 6.64 (s, 1H), 3.94 (t, 2H), 3.3 (s, 3H), 2.66 (d, 2H),2.56 (t, 2H), 2.14-2.04 (m, 1H), 1.99-1.9 (m, 2H), 1.63-1.42 (m, 5H),1.2-1.09 (m, 3H) “A266”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A267”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A268”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A269”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A270”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A271”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A272”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A273”5-(N-Phenyl-N-methylaminocarbonyl)-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A274”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A275”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A276”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-cyclocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A277”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A278”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A279”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A280”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A281”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A282”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A283”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A284”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A285”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A286”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A287”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A288”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A289”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A290”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A291”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A292”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A293”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A294”5-{N-[4-(2-dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A295”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A296”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A297”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A298”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A299”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A300”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-2.32 408 hydroxy-1H-indazole (P) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =11.96 (s, 1H, broad), 10.03 (s, 1H), 7.24 (s, 1H), 7.04 (d, 2H), 6.75(d, 2H), 6.64 (s, 1H), 3.29 (s, 3H), 3.04 (t, 4H), 2.62 (t, 2H), 2.38(t, 4H), 2.25 (s, 3H), 2.19 (s, 3H), 1.59-1.49 (m, 2H), 0.83 (t, 3H)“A301”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-propyl-6-2.7  409 hydroxy-1H-indazole (P) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =11.96 (s, 1H, broad), 9.76 (s, 1H), 7.26 (s, 1H), 7.16 (d, 2H), 7.14 (d,2H), 6.64 (s, 1H), 3.5 (t, 4H), 3.34 (s, 2H), 3.33 (s, 3H), 2.63 (t,2H), 2.24 (t, 4H), 1.61-1.51 (m, 2H), 0.84 (t, 3H) “A302”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-propyl-6- 1.79393 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] = 11.96(s, 1H, broad), 9.83 (s, 1H), 7.26 (s, 1H), 7.14 (d, 2H), 6.79 (d, 2H),6.64 (s, 1H), 3.95 (t, 2H), 3.3 (s, 3H), 2.65 (t, 2H), 2.56 (t, 2H),2.0-1.9 (m, 2H), 1.62-1.51 (m, 2H), 0.84 (t, 3H) “A303”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-1.22 409 hydroxy-1H-indazole (N) ¹H-NMR (DMSO-d₆, 80° C.): δ [ppm] =11.98 (s, 1H, broad), 9.77 (s, 1H), 7.34 (s, 1H), 7.29 (d, 2H), 7.25 (d,2H), 6.66 (s, 1H), 4.14 (s, 2H), 3.91 (t, 2H), 3.63 (t, 2H), 3.33 (s,3H), 2.68 (t, 2H), 1.65-1.55 (m, 2H), 0.85 (t, 3H) “A304”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A305”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A306”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A307”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A308”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A309”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A310”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A311”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl-(3-methylbutyl)-6-hydroxy-1H-indazole “A312”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A313”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A314”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A315”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A316”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A317”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A318”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A319”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A320”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A321”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A322”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A323”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A324”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A325”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A326”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole

The following examples relate to pharmaceutical compositions:

EXAMPLE A Injection Vials

A solution of 100 g of an active ingredient according to the inventionand 5 g of disodium hydrogenphosphate in 3 l of bidistilled water isadjusted to pH 6.5 using 2 N hydrochloric acid, sterile filtered,transferred into injection vials, lyophilised under sterile conditionsand sealed under sterile conditions. Each injection vial contains 5 mgof active ingredient.

EXAMPLE B Suppositories

A mixture of 20 g of an active ingredient according to the inventionwith 100 g of soya lecithin and 1400 g of cocoa butter is melted, pouredinto moulds and allowed to cool. Each suppository contains 20 mg ofactive ingredient.

EXAMPLE C Solution

A solution is prepared from 1 g of an active ingredient according to theinvention, 9.38 g of NaH₂PO₄.2H₂O, 28.48 g of Na₂HPO₄.12H₂O and 0.1 g ofbenzalkonium chloride in 940 ml of bidistilled water. The pH is adjustedto 6.8, and the solution is made up to 1 l and sterilised byirradiation. This solution can be used in the form of eye drops.

EXAMPLE D Ointment

500 mg of an active ingredient according to the invention are mixed with99.5 g of Vaseline under aseptic conditions.

EXAMPLE E Tablets

A mixture of 1 kg of active ingredient, 4 kg of lactose, 1.2 kg ofpotato starch, 0.2 kg of talc and 0.1 kg of magnesium stearate ispressed in a conventional manner to give tablets in such a way that eachtablet contains 10 mg of active ingredient.

EXAMPLE F Dragees

Tablets are pressed analogously to Example E and subsequently coated ina conventional manner with a coating of sucrose, potato starch, talc,tragacanth and dye.

EXAMPLE G Capsules

2 kg of active ingredient are introduced into hard gelatine capsules ina conventional manner in such a way that each capsule contains 20 mg ofthe active ingredient.

EXAMPLE H Ampoules

A solution of 1 kg of an active ingredient according to the invention in60 l of bidistilled water is sterile filtered, transferred intoampoules, lyophilised under sterile conditions and sealed under sterileconditions. Each ampoule contains 10 mg of active ingredient.

1. Compounds of the formula I

in which R¹ denotes H, OH, OCH₃, OCF₃, OCHF₂, OBzl, OAc,p-methoxybenzyloxy, SH, S(O)_(m)CH₃, SO₂NH₂, Hal, CF₃ or CH₃, R² denotesAlk, (CH₂)_(n)Het, CN, NO₂, NH₂, OH, OA, O(CH₂)_(n)Ar, O(CH₂)_(n)Het,SH, COA, CO(CH₂)_(n)Ar, CO(CH₂)_(n)Het, S(O)_(m)A, S(O)_(m)(CH₂)_(n)Ar,S(O)_(m)(CH₂)_(n)Het, NHA, NHAr, NHHet, NAA′, COOH, COOA, CONH₂, CONHA,CONAA′, CONH(CH₂)_(n)Ar, CONA(CH₂)_(n)Ar, CONH(CH₂)_(n)Het,CONA(CH₂)_(n)Het, SO₂NH₂, SO₂NHA, SO₂NAA′, SO₂NH(CH₂)_(n)Ar,SO₂NA(CH₂)_(n)Ar, SO₂NH(CH₂)_(n)Het, SO₂NA(CH₂)_(n)Het, NHCOA, NACOA′,NHCO(CH₂)_(n)Ar, NACO(CH₂)_(n)Ar, NHCO(CH₂)_(n)Het, NACO(CH₂)_(n)Het,NHSO₂A, NASO₂A′, NHSO₂(CH₂)_(n)Ar, NASO₂(CH₂)_(n)Ar, NHSO₂(CH₂)_(n)Het,NASO₂(CH₂)_(n)Het, NHCOOA, NHCOOAr, NHCOOHet, NHCONHA, NHCONHAr orNHCONHHet, R³ denotes H, Hal, A, AOH, COOA, CONH₂, CONHA, CONAA′,CONHAr, CONH(CH₂)Ar, CONAAr, CONA(CH₂)Ar, CONHHet, CONH(CH₂)Het,CONAHet, CONA(CH₂)Het, (CH₂)_(n)COOA, (CH₂)_(n)CONHA, (CH₂)_(n)CONAA′,(CH₂)_(n)NHCONH₂, (CH₂)_(n)NHCONHA, (CH₂)_(n)NHCONAA′, (CH₂)_(n)NHCOA,(CH₂)_(n)NHCOAr, (CH₂)_(n)NHSO₂A, -2-MERCK-3555 (CH₂)_(n)NHSO₂Ar,(CH₂)_(n)NASO₂Ar, (CH₂)_(n)NHSO₂CH₂Ar, (CH₂)_(n)NASO₂CH₂Ar, (CH₂)_(n)Ar,(CH₂)_(n)Het, NHAr or NHHet, Ar denotes phenyl, naphthyl or biphenyl,each of which is unsubstituted or mono-, di-, tri-, tetra- orpentasubstituted by A, OA, OH, SH, S(O)_(m)A, Hal, NO₂, CN, COA, COOH,COOA, CONR⁴R⁵, SO₂NR⁴R⁵, NR⁴R⁵, OCONR⁴R⁵, NR⁴COR⁵, NR⁴SO₂R⁵, NR⁴CONR⁴R⁵,(CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN, SO₂Het¹, O(CH₂)_(p)NR⁴R⁵ and/or(CH₂)_(m)Het¹, A, A′ each, independently of one another, denoteunbranched or branched alkyl having 1-10 C atoms, in which 1-3 CH₂groups may be replaced by O, S, SO, SO₂, NH, NMe or NEt and/or, inaddition, 1-5H atoms may be replaced by F and/or Cl, or denote Alk orcyclic alkyl having 3-8 C atoms, Alk denotes alkenyl or alkynyl having2-6 C atoms, Het denotes a mono- or bicyclic saturated, unsaturated oraromatic heterocycle having 1 to 4 N, O and/or S atoms, which may beunsubstituted or mono-, di- or trisubstituted by A, OA, OH, SH,S(O)_(m)A, Hal, NO₂, CN, COA, COOA, CONR⁴R⁵, SO₂NR⁴R⁵, NR⁴R⁵, OCONR⁴R⁵,NR⁴COR⁵, NR⁴SO₂R⁵, NR⁴CONR⁴R⁵, ═S, ═NH, ═NA and/or ═O (carbonyl oxygen),Het¹ denotes a monocyclic saturated heterocycle having 1 to 3 N and/or Oatoms, which may be unsubstituted or mono-, di- or trisubstituted by A,OA, OH and/or ═O (carbonyl oxygen), R⁴, R⁵ each, independently of oneanother, denote H or alkyl having 1-6 C atoms, in which 1-3 CH₂ groupsmay be replaced by O, S, SO, SO₂, NH, NMe, or NEt and/or, in addition,1-5H atoms may be replaced by F and/or Cl, Hal denotes F, Cl, Br or I, mdenotes 0, 1 or 2, n denotes 0, 1, 2, 3 or 4, p denotes 1, 2, 3 or 4,and pharmaceutically usable derivatives, salts, solvates andstereoisomers thereof, including mixtures thereof in all ratios. 2.Compounds according to claim 1 of the formula I in which R¹ denotes OHor OCH₃, and pharmaceutically usable derivatives, salts, solvates,tautomers and stereoisomers thereof, including mixtures thereof in allratios.
 3. Compounds according to claim 1 in which R² denotes CONH₂,CONHA, CONAA′, CONH(CH₂)_(n)Ar, CONA(CH₂)_(n)Ar, CONH(CH₂)_(n)Het orCONA(CH₂)_(n)Het, where A, A′ denotes alkyl having 1, 2, 3 or 4 C atomsor cyclic alkyl having 3-8 C atoms, and pharmaceutically usablederivatives, salts, solvates, tautomers and stereoisomers thereof,including mixtures thereof in all ratios.
 4. Compounds according toclaim 1 in which R³ denotes A or (CH₂)_(n)Ar, where Ar denotes phenylwhich is unsubstituted or mono-, di- or trisubstituted by A, Hal and/orOA, and pharmaceutically usable derivatives, salts, solvates, tautomersand stereoisomers thereof, including mixtures thereof in all ratios. 5.Compounds according to claim 1 in which Ar denotes phenyl which isunsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by A, OA,OH, CN, NH₂, NHA, NA₂, NHCOA, Hal, CONH₂, CONHA, CONAA′,(CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN, SO₂Het¹, O(CH₂)_(p)NH₂, O(CH₂)_(p)NA₂,O(CH₂)_(p)NHA and/or (CH₂)_(m)Het¹, and pharmaceutically usablederivatives, salts, solvates, tautomers and stereoisomers thereof,including mixtures thereof in all ratios.
 6. Compounds according toclaim 1 in which A, A′ each, independently of one another, denoteunbranched or branched alkyl having 1-6 C atoms, in which 1 or 2 CH₂groups may be replaced by O, NH, NMe or NEt and/or, in addition, 1-5Hatoms may be replaced by F and/or Cl, or denote cyclic alkyl having 3-8C atoms, and pharmaceutically usable derivatives, salts, solvates,tautomers and stereoisomers thereof, including mixtures thereof in allratios.
 7. Compounds according to claim 1 in which A, A′ each,independently of one another, denote unbranched or branched alkyl having1-6 C atoms, in which 1 CH₂ group may be replaced by O and/or, inaddition, 1-5H atoms may be replaced by F and/or Cl, or denote cyclicalkyl having 3-8 C atoms, and pharmaceutically usable derivatives,salts, solvates, tautomers and stereoisomers thereof, including mixturesthereof in all ratios.
 8. Compounds according to claim 1 in which Hetdenotes a mono- or bicyclic saturated, unsaturated or aromaticheterocycle having 1 to 3 N, O and/or S atoms, which may beunsubstituted or mono-, di- or trisubstituted by A, Hal, OH, OA, COA,═NH, ═NA and/or ═O (carbonyl oxygen), and pharmaceutically usablederivatives, salts, solvates, tautomers and stereoisomers thereof,including mixtures thereof in all ratios.
 9. Compounds according toclaim 1 in which Het denotes pyridyl, furyl, thienyl, pyrrolyl,oxazolyl, isoxazolyl, imidazolyl, pyrimidinyl, pyrazolyl, thiazolyl,pyrazinyl, pyridazinyl, pyrrolidinyl, piperidinyl, morpholinyl,piperazinyl, benzodioxanyl, benzodioxolyl, indolyl, quinolinyl,benzimidazolyl, benzothiadiazolyl, indazolyl, dihydrobenzimidazolyl,dihydroindolyl or tetrahydropyranyl, each of which is unsubstituted ormono-, di- or trisubstituted by A, Hal, OH, OA, COA and/or ═O (carbonyloxygen), and pharmaceutically usable derivatives, salts, solvates,tautomers and stereoisomers thereof, including mixtures thereof in allratios.
 10. Compounds according to claim 1 in which R¹ denotes OH orOCH₃, R² denotes CONH₂, CONHA, CONAA′, CONH(CH₂)_(n)Ar, CONA(CH₂)_(n)Ar,CONH(CH₂)_(n)Het or CONA(CH₂)_(n)Het, where A, A′ denotes alkyl having1, 2, 3 or 4 C atoms or cyclic alkyl having 3-8 C atoms, R³ denotes A or(CH₂)_(n)Ar, where Ar denotes phenyl which is unsubstituted or mono-,di- or trisubstituted by A, Hal and/or OA, Ar denotes phenyl which isunsubstituted or mono-, di-, tri-, tetra- or pentasubstituted by A, OA,OH, CN, NH₂, NHA, NA₂, NHCOA, Hal, CONH₂, CONHA, CONAA′,(CH₂)_(n)NHSO₂A, O(CH₂)_(p)CN, SO₂Het¹, O(CH₂)_(p)NH₂, O(CH₂)_(p)NA₂,O(CH₂)_(p)NHA and/or (CH₂)_(m)Het¹, A, A′ each, independently of oneanother, denote unbranched or branched alkyl having 1-6 C atoms, inwhich 1 CH₂ group may be replaced by O and/or, in addition, 1-5H atomsmay be replaced by F and/or Cl, or denote cyclic alkyl having 3-8 Catoms, and pharmaceutically usable derivatives, salts, solvates,tautomers and stereoisomers thereof, including mixtures thereof in allratios.
 11. Compounds according to claim 1 selected from the groupCompound No. Structure/name “A1” Methyl3-benzyl-6-hydroxy-1H-indazole-5-carboxylate “A2”3-Benzyl-6-hydroxy-1H-indazole-5-carboxylic acid “A3”5-Aminocarbonyl-3-benzyl-6-hydroxy-1H-indazole “A4”5-(N-Propyl-N-methylaminocarbonyl)-3-benzyl-6- hydroxy-1H-indazole “A5”5-(N-Butyl-N-methylaminocarbonyl)-3-benzyl-6- hydroxy-1H-indazole “A6”5-(N-Benzyl-N-methylaminocarbonyl)-3-benzyl-6- hydroxy-1H-indazole “A7”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole  

“A8” 5-[N-(3-Methylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole  

“A9” 5-[N-(2-Chlorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A10”5-[N-(3-Chlorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A11”5-[N-(2-Fluorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A12”5-[N-(3-Fluorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A13”5-[N-(2-Bromobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A14”5-[N-(2-Methylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A15”5-[N-(4-Fluorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A16”5-[N-(2-Methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A17”5-[N-(4-Methylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A18”5-[N-(4-Chlorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A19”5-[N-(3,4-Dichlorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A20” 5-[N-(2-Methoxy-5-methylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A21”5-[N-(2,4-Dimethylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A22”5-[N-(4-Ethoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A23”5-[N-(2,3-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A24”5-[N-(4-Bromobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A25”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-methylphenyl)-6-hydroxy-1H-indazole “A26” 5-[N-(3-Bromobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A27”5-[N-(3-Methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A28”5-[N-(4-Ethylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A29” 5-[N-(3-Trifluoromethylbenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A30”5-[N-(Benzo-1,3-dioxol-4-ylmethyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A31”5-[N-(3-Chloro-6-methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A32”5-(N-Benzyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H-indazole “A33”5-(N-Butyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H-indazole “A34”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(2-chlorobenzyl)-6-hydroxy-1H-indazole “A35”5-(N-Propyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H-indazole “A36”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A37”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A38”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A39”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A40”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A41”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A42”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A43”5-(N-Butyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H-indazole “A44”5-(N-Benzyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H-indazole “A45”5-[N-(2-Methoxyethyl)-N-methylaminocarbonyl]-3-(2-methylbenzyl)-6-hydroxy-1H-indazole “A46”5-(N-Propyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H-indazole “A47”5-[N-(Furan-2-ylmethyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A48” 5-[N-(4-Chloro-3-methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A49”5-[N-(3,4-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A50”5-[N-(4-Methoxybenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A51”5-[N-(4-Chloro-3-fluorobenzyl)-N-methylaminocarbonyl]-3-benzyl-6-hydroxy-1H-indazole “A52”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-1H-indazole “A53”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-1H-indazole “A54”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methylbenzyl)-6-hydroxy-1H-indazole “A55”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H-indazole “A56”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H-indazole “A57”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H-indazole “A58”5-(N-Butyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H-indazole “A59”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H-indazole “A60”5-(N-Propyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H-indazole “A61”5-(N-Butyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H-indazole “A62”5-(N-Benzyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H-indazole “A63”5-(N-Propyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H-indazole “A64”5-(N-Butyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H-indazole “A65”5-(N-Benzyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H-indazole “A66”5-(N-Propyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H-indazole “A67”5-(N-Propyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-indazole “A68”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-indazole “A69”5-(N-Butyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-indazole “A70”5-(N-Butyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H-indazole “A71”5-(N-Benzyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H-indazole “A72”5-(N-Propyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H-indazole “A73”5-(N-Propyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-indazole “A74”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-indazole “A75”5-(N-Butyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-indazole “A76”5-[N-(4-Chloro-3-methoxybenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6- hydroxy-1H-indazole “A77”5-[N-(3,4-Dimethoxybenzyl)-N- methylaminocarbonyl]3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A78”5-[N-(4-Methoxybenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A79”5-[N-(Benzo-1,3-dioxol-5-ylmethyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6- hydroxy-1H-indazole “A80”5-[N-(3-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A81”5-[N-(2-Bromobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A82”5-[N-(2,3-Dihydrobenzo-1,4-dioxin-6-ylmethyl)-N-methyl-aminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole  

“A83” 5-[N-(4-Chloro-3-fluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6- hydroxy-1H-indazole “A84”5-[N-(3-Methylsulfonylaminobenzyl)-N-methylamino-carbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A85”5-[N-(3-Methylsulfonylaminomethylbenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6- hydroxy-1H-indazole “A86”5-(N-Benzyl-N-ethylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A87”5-[N-(2,4-Difluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A88”5-[N-(4-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A89”5-[N-(Furan-2-ylmethyl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A90”5-[N-(2-Bromobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A91”5-[N-(3-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A92”5-[N-(4-Methylbenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A93”5-[N-(4-Chlorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A94”5-[N-(4-Ethylbenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A95”5-[N-(2,3-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A96”5-[N-(Benzo-1,3-dioxol-5-ylmethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A97”5-[N-(4-Methylbenzyl)-N-ethylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A98”5-[N-(4-Chloro-3-methoxybenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A99”5-[N-(3,4-Dimethoxybenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A100”5-[N-(4-Methoxybenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A101”5-[N-(2,3-Dihydrobenzo-1,4-dioxin-6-ylmethyl)-N-methyl-aminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A102”5-[N-(4-Chloro-3-fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A103”5-(N-Benzyl-N-ethylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A104”5-[N-(3-Methylsulfonylaminobenzyl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A105”5-[N-(4-Methylsulfonylaminomethylbenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A106”5-[N-(4-Methylsulfonylaminobenzyl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A107”5-[N-(2,4-Difluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A108”5-[N-(4-Fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A109”5-[N-(4-Chloro-2-fluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A110”5-[N-(3,4-Difluorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A111”5-(N-Benzyl-N-methylaminocarbonyl)-3-(3-methoxybenzyl)-6-hydroxy-1H-indazole “A112”5-[N-(4-Chlorobenzyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A113”5-[N-(4-Methylbenzyl)aminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A114”5-[N-(Furan-2-ylmethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A115”5-(N-Benzylaminocarbonyl)-3-(3-methylbenzyl)-6- hydroxy-1H-indazole“A116” 5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A117”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A118”5-(N-Phenyl-N-methylaminocarbonyl)-3- benzyl-6-hydroxy-1H-indazole“A119” 5-(N-Phenyl-N-methylaminocarbonyl)-3-(2-methylbenzyl)-6-hydroxy-1H-indazole “A120”5-(N-Phenyl-N-methylaminocarbonyl)-3-(2-chlorobenzyl)-6-hydroxy-1H-indazole “A121”5-(N-Phenyl-N-methylaminocarbonyl)-3-(4-chlorobenzyl)-6-hydroxy-1H-indazole “A122”5-(N-Phenyl-N-methylaminocarbonyl)-3-(4-methylbenzyl)-6-hydroxy-1H-indazole “A123”5-(N-Phenyl-N-methylaminocarbonyl)-3-(4-ethylbenzyl)-6-hydroxy-1H-indazole “A124”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3,4-dichlorobenzyl)-6-hydroxy-1H-indazole “A125”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3,4-dimethylbenzyl)-6-hydroxy-1H-indazole “A126”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-fluoro-5-methyl-benzyl)-6-hydroxy-1H-indazole “A127”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-fluorobenzyl)-6-hydroxy-1H-indazole “A128”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-ethylbenzyl)-6-hydroxy-1H-indazole “A129”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-methoxybenzyl)-6-hydroxy-1H-indazole “A130”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A131”5-[N-(2-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A132”5-[N-(2-Chlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A133”5-[N-(2-Fluorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A134”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A135”5-[N-(3-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A136”5-[N-(4-Chlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A137”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A138”5-[N-(3-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A139”5-[N-(4-Fluorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A140”5-[N-(4-Trifluoromethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)- 6-hydroxy-1H-indazole “A141”5-[N-(3-Chlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A142”5-[N-(3,4-Dichlorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A143”5-[N-(2,3-Dihydrobenzo-1,4-dioxin-6-yl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A144”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A145”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A146”5-[N-(4-Chloro-3-methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A147”5-[N-(3-Chloro-4-methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A148”5-[N-(4-Acetylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A149”5-[N-(3-Acetylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A150”5-[N-(4-Methylsulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A151”5-[N-(2,2-Difluorobenzo-1,3-dioxol-5-yl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A152”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A153”5-[N-(3-Fluorophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A154”5-[N-(3-Trifluoromethoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A155”5-[N-(3-Trifluoromethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A156”5-[N-(3-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A157”5-[N-(1-Acetyl-2,3-dihydro-1H-indol-5-yl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole  

“A158” 5-[N-(1-Acetyl-2,3-dihydro-1H-indol-6-yl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A159”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6-hydroxy-1H-indazole “A160”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6-hydroxy-1H-indazole “A161”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6-hydroxy-1H-indazole “A162”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6- hydroxy-1H-indazole “A163”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-methoxybenzyl)-6-hydroxy-1H-indazole “A164”5-(N-Benzyl-N-methylaminocarbonyl)-3-butyl-6- hydroxy-1H-indazole “A165”5-(N-Phenyl-N-methylaminocarbonyl)-3-ethyl-6- hydroxy-1H-indazole “A166”5-(N-Phenyl-N-methylaminocarbonyl)-3-butyl-6- hydroxy-1H-indazole “A167”5-(N-Phenyl-N-methylaminocarbonyl)-3-propyl-6- hydroxy-1H-indazole“A168” 5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A169”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A170”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-butyl-6- hydroxy-1H-indazole “A171”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A172”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A173”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A174”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A175”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A176”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A177”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylamino-carbonyl]-3-propyl-6-hydroxy-1H-indazole “A178”5-(N-Benzyl-N-methylaminocarbonyl)-3-propyl-6-hydroxy- 1H-indazole“A179” 5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A180”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A181”5-(N-Benzyl-N-methylaminocarbonyl)-3-phenethyl-6- hydroxy-1H-indazole“A182” 5-(N-Propyl-N-methylaminocarbonyl)-3-phenethyl-6-hydroxy-1H-indazole “A183”5-(N-Butyl-N-methylaminocarbonyl)-3-phenethyl-6- hydroxy-1H-indazole“A184” 5-[N-(Tetrahydropyran-4-yl)-N-methylaminocarbonyl]-3-(3-chlorobenzyl)-6-hydroxy-1H-indazole “A185”5-[N-(Piperidin-4-yl)-N-methylaminocarbonyl]-3-(3-chloro-benzyl)-6-hydroxy-1H-indazole “A186”5-[N-(Tetrahydropyran-4-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A187”5-[N-(Piperidin-4-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A188”5-[N-(Cyclopropylmethyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A189”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A190”5-{N-[3-Methoxy-4-(4-methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A191”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole  

“A192” 5-[N-(4-Bromophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A193”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A194”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A195”5-(N-Cyclohexyl-N-methylaminocarbonyl)-3-(3-methyl-benzyl)-6-hydroxy-1H-indazole “A196”5-[N-(1-Methylpiperidin-4-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A197”5-[N-(4-Dimethylaminophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A198”5-[N-(4-Aminocarbonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A199”5-[N-(3-Methylsulfonylaminophenyl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A200”5-[N-(4-Acetamidophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A201”5-[N-(3-Acetamidophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A202”5-[N-(3-Aminocarbonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A203”5-[N-(3-Aminosulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A204”5-[N-(4-Aminosulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A205”5-[N-(4-Cyanophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A206”5-[N-(3-Cyanophenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A207”5-[N-(2-Oxo-2,3-dihydro-1H-benzimidazol-5-yl)-N-methyl-aminocarbonyl]-3-(3-methylbenzyl)-6- hydroxy-1H-indazole  

“A208” 5-{N-[4-Methoxy-3-(4-methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A209”5-[N-(3-Methylsulfonylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A210”5-{N-[4-(Morpholine-4-sulfonyl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6- hydroxy-1H-indazole “A211”5-[N-(3H-Benzimidazol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole  

“A212” 5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole  

“A213” 5-{N-[4-(2-Oxomorpholin-4-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A214”5-{N-[4-(2-Oxopiperazin-1-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A215”5-{N-[4-(2-Oxo-1,3-oxazinan-3-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole  

“A216” 5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole  

“A217” 5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A218”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A219”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A220”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylamino-carbonyl}-3-(3-methylbenzyl)-6-hydroxy-1H-indazole “A221”5-(N-Phenyl-N-methylaminocarbonyl)-3-isobutyl-6- hydroxy-1H-indazole“A222” 5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A223”5-[N-(4-Methoxphenyl)-N-methylaminocarbony1]-3-isobutyl-6-hydroxy-1H-indazole “A224”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A225”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A226”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A227”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A228”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylamino-carbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A229”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A230”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A231”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylamino-carbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A232”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A233”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A234”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A235”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A236”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-isobutyl-6-hydroxy-1H-indazole “A237”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-isobutyl-6-hydroxy-1H-indazole “A238”5-(N-Phenyl-N-methylaminocarbonyl)-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A239”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A240”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A241”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A242”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A243”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A244”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A245”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A246”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A247”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A248”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A249”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A250”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A251”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A252”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A253”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopropylmethyl-6-hydroxy-1H-indazole “A254”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopropylmethyl-6- hydroxy-1H-indazole “A255”5-(N-Phenyl-N-methylaminocarbonyl)-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A256”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A257”5-[N-(3-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A258”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A259”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A260”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A261”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A262”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A263”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A264”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A265”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A266”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A267”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A268”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A269”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A270”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A271”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclopentylmethyl-6-hydroxy-1H-indazole “A272”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclopentylmethyl-6- hydroxy-1H-indazole “A273”5-(N-Phenyl-N-methylaminocarbonyl)-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A274”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A275”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A276”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A277”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A278”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A279”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A280”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A281”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A282”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A283”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A284”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N- methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A285”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A286”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A287”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A288”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-cyclohexylmethyl-6-hydroxy-1H-indazole “A289”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-cyclohexylmethyl-6- hydroxy-1H-indazole “A290”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A291”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-butyl-6-hydroxy-1H-indazole “A292”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A293”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A294”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-butyl-6- hydroxy-1H-indazole “A295”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A296”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A297”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-butyl-6-hydroxy-1H-indazole “A298”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-butyl-6-hydroxy-1H-indazole “A299”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-butyl-6-hydroxy-1H-indazole “A300”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A301”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-propyl-6-hydroxy-1H-indazole “A302”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A303”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A304”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A305”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A306”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A307”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-propyl-6-hydroxy-1H-indazole “A308”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-propyl-6-hydroxy-1H-indazole “A309”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-propyl-6-hydroxy-1H-indazole “A310”5-(N-Phenyl-N-methylaminocarbonyl)-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A311”5-[N-(4-Methylphenyl)-N-methylaminocarbonyl-(3-methylbutyl)-6-hydroxy-1H-indazole “A312”5-[N-(4-Methoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A313”5-[N-(4-Methylsulfonylaminomethylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6- hydroxy-1H- indazole “A314”5-[N-(Benzo-1,3-dioxol-5-yl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A315”5-[N-(3,4-Dimethoxyphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A316”5-[N-(4-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A317”5-{N-[4-(4-Methylpiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6- hydroxy-1H-indazole “A318”5-[N-(4-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A319”5-{N-[4-(3-Cyanopropoxy)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6- hydroxy-1H-indazole “A320”5-{N-[4-(3-Oxomorpholin-4-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6- hydroxy-1H-indazole “A321”5-{N-[4-(2-Dimethylaminoethoxy)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6- hydroxy-1H-indazole “A322”5-{N-[4-(3-Oxopiperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6- hydroxy-1H-indazole “A323”5-{N-[4-(Piperazin-1-yl)phenyl]-N-methylaminocarbonyl}-3-(3-methylbutyl)-6- hydroxy-1H-indazole “A324”5-[N-(3-Morpholin-4-ylmethylphenyl)-N-methylamino-carbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A325”5-[N-(3-Morpholin-4-ylphenyl)-N-methylaminocarbonyl]-3-(3-methylbutyl)-6-hydroxy-1H-indazole “A326”5-{N-[3-(4-Methylpiperazin-1-yl)phenyl]-N-methylamino-carbonyl}-3-butyl-6-hydroxy-1H-indazole

and pharmaceutically usable derivatives, salts, solvates andstereoisomers thereof, including mixtures thereof in all ratios. 12.Process for the preparation of compounds of the formula I according toclaim 1 and pharmaceutically usable derivatives, solvates, salts andstereoisomers thereof, characterised in that a) a compound of theformula II

in which R¹, R² and R³ have the meanings indicated in claim 1, and Ldenotes F, Cl, Br, I or a free or reactively modified OH group, isreacted with hydrazine or hydrazine hydrate, one or more radical(s) R¹,R² and/or R³ are subsequently, if desired, converted into one or moreradical(s) R¹, R² and/or R³ by, for example, i) reducing a nitro groupto an amino group, ii) hydrolysing an ester group to a carboxyl group,iii) converting an amino group into an alkylated amine by reductiveamination, iv) converting a carboxyl group or an ester into an amide, v)acylating an amino group, and/or a base or acid of the formula I isconverted into one of its salts.
 13. Medicaments comprising at least onecompound according to claim 1 and/or pharmaceutically usablederivatives, solvates and stereoisomers thereof, including mixturesthereof in all ratios, and optionally excipients and/or adjuvants.
 14. Amethod for the treatment and/or prophylaxis of diseases in which theinhibition, regulation and/or modulation of HSP90 plays a role,comprising administering to a patient an effective amount of a compoundaccording to claim
 1. 15. A method according to claim 14 for thepreparation of a medicament for the treatment or prevention of tumourdiseases, viral diseases, for immune suppression in transplants,inflammation-induced diseases, cystic fibrosis, diseases associated withangiogenesis, infectious diseases, autoimmune diseases, ischaemia,fibrogenetic diseases, for the promotion of nerve regeneration, forinhibiting the growth of cancer, tumour cells and tumour metastases, forthe protection of normal cells against toxicity caused by chemotherapy,for the treatment of diseases in which incorrect protein folding oraggregation is a principal causal factor.
 16. A method according toclaim 15, where the tumour diseases are fibrosarcoma, myxosarcoma,liposarcoma, chondrosarcoma, osteogenic sarcoma, chordoma, angiosarcoma,endotheliosarcoma, lymphangiosarcoma, lymphangioendotheliosarcoma,synovioma, mesothelioma, Ewing's tumour, leiosarcoma, rhabdomyosarcoma,colon carcinoma, pancreatic cancer, breast cancer, ovarian cancer,prostate cancer, squamous cell carcinoma, basal cell carcinoma,adenocarcinoma, syringocarcinoma, sebaceous gland carcinoma, papillarycarcinoma, papillary adenocarcinomas, cystadenocarcinomas, bone marrowcarcinoma, bronchogenic carcinoma, renal cell carcinoma, hepatoma, bileduct carcinoma, choriocarcinoma, seminoma, embryonic carcinoma, Wilm'stumour, cervical cancer, testicular tumour, lung carcinoma, small-celllung carcinoma, bladder carcinoma, epithelial carcinoma, glioma,astrocytoma, medulloblastoma, craniopharyngioma, ependymoma, pinealoma,haemangioblastoma, acoustic neuroma, oligodendroglioma, meningioma,melanoma, neuroblastoma, retinoblastoma, leukaemia, lymphoma, multiplemyeloma, Waldenstrom's macroglobulinaemia and heavy chain disease.
 17. Amethod according to claim 15, where the viral pathogen of the viraldiseases is selected from the group consisting of hepatitis type A,hepatitis type B, hepatitis type C, influenza, varicella, adenovirus,herpes simplex type I (HSV-I), herpes simplex type II (HSV-II), cattleplague, rhinovirus, echovirus, rotavirus, respiratory syncytial virus(RSV), papillomavirus, papovavirus, cytomegalovirus, echinovirus,arbovirus, huntavirus, Coxsackie virus, mumps virus, measles virus,rubella virus, polio-virus, human immunodeficiency virus type I (HIV-I)and human immunodeficiency virus type II (HIV-II).
 18. A methodaccording to claim 15, where the inflammation-induced diseases arerheumatoid arthritis, asthma, multiple sclerosis, type 1 diabetes, lupuserythematosus, psoriasis and inflammatory bowel disease.
 19. A methodaccording to claim 15, where the diseases associated with angiogenesisare diabetic retinopathy, haemangiomas, endometriosis and tumourangiogenesis.
 20. A method according to claim 15, where the fibrogeneticdiseases are sclerodermatitis, polymyositis, systemic lupus, cirrhosisof the liver, keloid formation, interstitial nephritis and pulmonaryfibrosis.
 21. A method according to claim 15, where the diseases inwhich incorrect protein folding or aggregation is a principal causalfactor are scrapie, Creutzfeldt-Jakob disease, Huntington's orAlzheimer's.
 22. Medicaments comprising at least one compound accordingto claim 1 and/or pharmaceutically usable derivatives, solvates andstereoisomers thereof, including mixtures thereof in all ratios, and atleast one further medicament active ingredient.
 23. Set (kit) consistingof separate packs of (a) an effective amount of a compound according toclaim 1 and/or pharmaceutically usable derivatives, solvates andstereoisomers thereof, including mixtures thereof in all ratios, and (b)an effective amount of a further medicament active ingredient.